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Pathogenic bacteria, intestinal infection, tuberculosis, enteritis, foodborne illness, tuberculous meningitis, tuberculous gumma, tuberculous ly [...]




PATHOGENIC BACTERIA


Pathogenic bacteria are bacteria that cause infectious diseases. This article deals with human pathogenic bacteria.

Although the vast majority of bacteria are harmless or beneficial, quite a few bacteria are pathogenic. One of the bacterial diseases with highest disease burden is tuberculosis, caused by the bacterium Mycobacterium tuberculosis, which kills about 2 million people a year, mostly in sub-Saharan Africa. Pathogenic bacteria contribute to other globally important diseases, such as pneumonia, which can be caused by bacteria such as Streptococcus and Pseudomonas, and foodborne illnesses, which can be caused by bacteria such as Shigella, Campylobacter and Salmonella . Pathogenic bacteria also cause infections such as tetanus, typhoid fever, diphtheria, syphilis and leprosy.

History

Koch's postulates, proposed by Robert Koch in 1890, are criteria designed to establish a causal relationship between a causative microbe and a disease.

Diseases

Each pathogenic species has a characteristic spectrum of interactions with its human hosts.

Conditionally pathogenic

Some organisms, such as Staphylococcus or Streptococcus, can cause skin infections, pneumonia, meningitis and even overwhelming sepsis, a systemic inflammatory response producing shock, massive vasodilation and death.

Yet these organisms are also part of the normal human flora and usually exist on the skin or in the nose without causing disease.

Intracellular

Other organisms invariably cause disease in humans, such as the Rickettsia, which are obligate intracellular parasites able to grow and reproduce only within the cells of other organisms. One species of Rickettsia causes typhus, while another causes Rocky Mountain spotted fever.

Chlamydia, another phylum of obligate intracellular parasites, contains species that can cause pneumonia, or urinary tract infection and may be involved in coronary heart disease.

Mycobacterium and Brucella can exist intracellularly, though they are facultative (not obligate intracellular parasites.)

Opportunistic

Some species of bacteria, such as Pseudomonas aeruginosa, Burkholderia cenocepacia, and Mycobacterium avium, are opportunistic pathogens and cause disease mainly in people suffering from immunosuppression or cystic fibrosis.

Treatment


: See also overview list below

Bacterial infections may be treated with antibiotics, which are classified as bacteriocidal if they kill bacteria, or bacteriostatic if they just prevent bacterial growth. There are many types of antibiotics and each class inhibits a process that is different in the pathogen from that found in the host. For example, the antibiotics chloramphenicol and tetracyclin inhibit the bacterial ribosome, but not the structurally-different eukaryotic ribosome, and so exhibit selective toxicity. Antibiotics are used both in treating human disease and in intensive farming to promote animal growth. Both uses may be contributing to the rapid development of antibiotic resistance in bacterial populations. Infections can be prevented by antiseptic measures such as sterilizing the skin prior to piercing it with the needle of a syringe, and by proper care of indwelling catheters. Surgical and dental instruments are also sterilized to prevent constapation and infection by bacteria. Disinfectants such as bleach are used to kill bacteria or other pathogens on surfaces to prevent contamination and further reduce the risk of infection. Most bacteria in food are killed by cooking to temperatures above 73 °C (163°F).

Basic laboratory characteristics

The following genera contain the most important human pathogenic bacteria species: and species


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! Genus
! Important species
! Gram staining
! Shape
! Capsulation
! Bonding tendency
! Motility
! Respiration
! Growth medium
! Intra/Extracellular


Bordetella
Bordetella pertussis
Gram-negative
Small coccobacilli
Encapsulated
singly or in pairs
aerobic
Regan-Lowe agar
extracellular


Borrelia
Borrelia burgdorferi
Gram-negative, but stains poorly
Long, slender, flexible, spiral- or corkscrew-shaped rods
highly motile
(difficult to culture)
extracellular


Brucella
Brucella abortus
Brucella canis
Brucella melitensis
Brucella suis
Gram-negative
Small coccobacilli
Unencapsulated
singly or in pairs
aerobic
Blood agar
intracellular


Campylobacter
Campylobacter jejuni
Gram-negative
Curved, spiral, or S-shaped
with single, polar flagellum
characteristic darting motion
microaerophilic
Blood agar inhibiting other fecal flora
extracellular


Chlamydia
Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia trachomatis
(not Gram-stained)
Small, round, ovoid
motile
Facultative or strictly aerobic
Obligate intracellular


Clostridium
Clostridium botulinum
Clostridium difficile
Clostridium perfringens
Clostridium tetani
Gram-positive
Large, blunt-ended rods
mostly motile
Obligate anaerobic
Anaerobic blood agar
extracellular


Corynebacterium
Corynebacterium diphtheriae
Gram-positive (unevenly)
Small, slender, pleomorphic rods
unencapsulated
clumps looking like Chinese characters or a picket fence
nonmotile
Mostly facultative anaerobic
Aerobically on Tinsdale agar
extracellular


Enterococcus
Enterococcus faecalis
Enterococcus faecium
Gram-positive
Round to ovoid
pairs or chains
Facultative Anaerobic
6.5% NaCl, bile-esculin agar
extracellular


Escherichia
Escherichia coli
Gram-negative
Short rods
Facultative anaerobic
MacConkey agar
extracellular


Francisella
Francisella tularensis
Gram-negative
Small, pleomorphic coccobacillus
strictly aerobic
(rarely cultured)
Facultative intracellular


Haemophilus
Haemophilus influenzae
Gram-negative
Ranging from small coccobacillus to long, slender filaments
Chocolate agar with hemin and NAD +
extracellular


Helicobacter
Helicobacter pylori
Gram-negative
Curved or spiral rods
pultiple polar flagella
rapid, corkscrew motility
Medium containing antibiotics against other fecal flora
extracellular


Legionella
Legionella pneumophila
Gram-negative, but stains poorly
Slender rod in nature, cocobacillary in laboratory.
monotrichious flagella
unencapsulated
motile
Specialized medium
facultative intracellular


Leptospira
Leptospira interrogans
Gram-negative, but stains poorly
Long, very slender, flexible, spiral- or corkscrew-shaped rods
highly motile
Specialized medium
extracellular


Listeria
Listeria monocytogenes
Gram-positive, darkly
Slender, short rods
diplobacilli or short chains
Distinct tumbling motility in liquid medium
enriched medium
intracellular


Mycobacterium
Mycobacterium leprae
Mycobacterium tuberculosis
(none)
Long, slender rods
nonmotile
aerobic
M. tuberculosis: Lowenstein-Jensen agar
M. leprae: (none)
extracellular


Mycoplasma
Mycoplasma pneumoniae
(none)
Plastic, pleomorphic
singly or in pairs
(rarely cultured)
extracellular


Neisseria
Neisseria gonorrhoeae
Neisseria meningitidis
Gram-negative
Kidney bean-shaped
diplococci
aerobic
Thayer-Martin agar
Gonococcus : facultative intracellular
N. meningitidis : extracellular


Pseudomonas
Pseudomonas aeruginosa
Gram-negative
rods
encapsulated
motile
Obligate aerobic
MacConkey agar
extracellular


Rickettsia
Rickettsia rickettsii
Gram-negative, but stains poorly
Small, rod-like coccobacillary
(rarely cultured)
Obligate intracellular


Salmonella
Salmonella typhi
Salmonella typhimurium
Gram-negative
Facultative anaerobic
MacConkey agar
Facultative intracellular


Shigella
Shigella sonnei
Gram-negative
rods
Facultative anaerobic
Hektoen agar
extracellular


Staphylococcus
Staphylococcus aureus
Staphylococcus epidermidis
Staphylococcus saprophyticus
Gram-positive, darkly
Round cocci
in bunches like grapes
Facultative anaerobic
enriched medium (broth and/or blood)
extracellular


Streptococcus
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Gram-positive
ovoid to spherical
pairs or chains
nonmotile
Facultative anaerobic
blood agar
extracellular


Treponema
Treponema pallidum
Gram-negative, but stains poorly
Long, slender, flexible, spiral- or corkscrew-shaped rods
highly motile
none
extracellular


Vibrio
Vibrio cholerae
Gram-negative
Short, curved, rod-shaped with single polar flagellum
rapidly motile
Facultative anaerobic
blood- or MacConkey agar. Stimulated by NaCl
extracellular


Yersinia
Yersinia pestis
Gram-negative, stains bipolarly
Small rods
encapsulated
nonmotile
Facultative Anaerobe
MacConkey or CIN agar
extracellular


Clinical characteristics

This is a rather clinical description of the species presented in the previous section, containing the main examples of transmission, diseases, treatment, prevention and laboratory diagnosis, which all can differ substantially among the species of the same genus.

See also

Bacteria
Disease
Pathogen
Human flora
Human microbiome project
Pathogenic viruses

References



TUBERCULOSIS

Tuberculosis or TB (short for tubercles bacillus) is a common and often deadly infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis in humans. Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air, when people who have the disease cough, sneeze, or spit . Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of its victims.

The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. Infection of other organs causes a wide range of symptoms. Diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as microscopic examination and microbiological culture of bodily fluids. Treatment is difficult and requires long courses of multiple antibiotics. Contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in ( extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination, usually with Bacillus Calmette-Guérin vaccine.

A third of the world's population are thought to be infected with M. tuberculosis, and new infections occur at a rate of about one per second. The proportion of people who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing. In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in developing countries. In addition, more people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5-10% of the US population test positive.

Classification

The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.

Signs and symptoms

Health. Author: George Schiffman, MD, FCCP. Last Editorial Review: 1/15/2009 with many symptoms overlapping with other variants, while others are more (but not entirely) specifc for certain variants. Multiple variants may be present simultaneously.
Phylogenetic tree of the genus Mycobacterium .

When the disease becomes active, 75% of the cases are pulmonary TB, that is, TB in the lungs. Symptoms include chest pain, coughing up blood, and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, pallor, and often a tendency to fatigue very easily. This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculosis pleurisy, the central nervous system in meningitis, the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and bones and joints in Pott's disease of the spine. An especially serious form is disseminated TB, more commonly known as miliary tuberculosis. Extrapulmonary TB may co-exist with pulmonary TB as well. Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated August 2003.

Causes

The primary cause of TB, Mycobacterium tuberculosis, is a small aerobic non-motile bacillus. High lipid content of this pathogen accounts for many of its unique clinical characteristics. It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour. (For example, one of the fastest-growing bacteria is a strain of E. coli that can divide roughly every 20 minutes.) Since MTB has a cell wall but lacks a phospholipid outer membrane, it is classified as a Gram-positive bacterium. However, if a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall. MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in vitro .

Using histological stains on expectorate samples from phlegm (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB). The most common acid-fast staining technique, the Ziehl-Neelsen stain, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an auramine-rhodamine stain and fluorescent microscopy.

The M. tuberculosis complex includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti and M. microti . M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis. M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries. M. microti is mostly seen in immunodeficient people, although it is possible that the prevalence of this pathogen has been underestimated.

Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium and M. kansasii . The last two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB.

Risk factors

Persons with silicosis have an approximately 30-fold greater risk for developing TB. CDC, Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection, Table 3 Silica particles irritate the respiratory system, causing immunogenic responses such as phagocytosis which consequently results in high lymphatic vessel deposits. It is this interference and blockage of macrophage function which increases the risk of tuberculosis. Persons with chronic renal failure who are on hemodialysis also have an increased risk: 10—25 times greater than the general population. Persons with diabetes mellitus have a risk for developing active TB that is two to four times greater than persons without diabetes mellitus, and this risk is likely greater in persons with insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB include gastrectomy with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia).

Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various (indoor) air pollutants on the disease would be necessary. Some possible indoor source of silica includes paint, concrete and Portland cement. Crystalline silica is found in concrete, masonry, sandstone, rock, paint, and other abrasives. The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine silica dust. It can also be in soil, mortar, plaster, and shingles. When you wear dusty clothing at home or in your car, you may be carrying silica dust that your family will breathe.

Low body weight is associated with risk of tuberculosis as well. A body mass index (BMI) below 18.5 increases the risk by 2—3 times. On the other hand, an increase in body weight lowers the risk. Patients with diabetes mellitus are at increased risk of contracting tuberculosis,

Other conditions that increase risk include IV drug abuse; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; prolonged corticosteroid therapy and other immunosuppressive therapy; Immunocompromised patients (30-40% of AIDS patients in the world also have TB) hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney disease; intestinal bypass; chronic malabsorption syndromes; vitamin D deficiency; and low body weight.

Twin studies in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then the other was more likely to get TB if he was identical than if he was not. These findings were more recently confirmed by a series of studies in South Africa. Specific gene polymorphisms in IL12B have been linked to tuberculosis susceptibility.

Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB.

Mechanism

Transmission

When people suffering from active pulmonary TB cough, sneeze, speak, or spit, they expel infectious aerosol droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets.

People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10-15 other people per year. Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.

Transmission can only occur from people with active — not latent — TB . The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain. The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others.
TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle. (See details below.)

Pathogenesis

About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease.

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus, and is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe . Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. Further spread is through the bloodstream to other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone. All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.

Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected. Cytotoxic T cells can also directly kill infected cells, by secreting perforin and granulysin.

Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis.

If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a fatality rate near 100% if untreated. However, If treated early, the fatality rate is reduced to near 10%.

In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.

If untreated, infection with Mycobacterium tuberculosis can become lobar pneumonia.

Diagnosis

Tuberculosis is diagnosed definitively by identifying the causative organism ( Mycobacterium tuberculosis ) in a clinical sample (for example, sputum or pus). When this is not possible, a probable - although sometimes inconclusive - diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test (Mantoux test).

The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must include a medical history, a physical examination, a chest X-ray, microbiological smears, and cultures. It may also include a tuberculin skin test, a serological test. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppression.

Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to an extract made from M. tuberculosis . Tuberculin tests have the disadvantage of producing false negatives, especially when the patient is co-morbid with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease. The newer interferon release assays (IGRAs) overcome many of these problems. IGRAs are in vitro blood tests that are more specific than the skin test. IGRAs detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6. These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results.

New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include polymerase chain reaction assays for the detection of bacterial DNA. The development of a rapid and inexpensive diagnostic test would be particularly valuable in the developing world.

Prevention

TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are vaccinated to protect them from TB. No vaccine is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria gives some protection against TB.

The World Health Organization (WHO) declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015. World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006. Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible. This goal would be helped greatly by an effective vaccine.

Vaccines

Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control programmes, especially for infants. According to the WHO, this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in 1993. This was the first vaccine for TB and developed at the Pasteur Institute in France between 1905 and 1921. However, mass vaccination with BCG did not start until after World War II. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%. However, BCG is less effective in areas where mycobacteria are less prevalent; therefore BCG is not given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria:
Infants or children with negative skin test results who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to multidrug-resistant TB.
Healthcare workers considered on an individual basis in settings in which a high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were not successful.

BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people with HIV.

Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans. A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group led by Oxford University, and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines (fusion molecules composed of two recombinant proteins delivered in an adjuvant) such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles, making them preferable for areas where HIV is very common. All of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.

Screening

Mantoux tuberculin skin tests are often used for routine screening of high risk individuals.

Interferon-γ release assays are blood tests used in the diagnosis of some infectious diseases. There are currently two interferon-γ release assays available for the diagnosis of tuberculosis:
QuantiFERON-TB Gold (licensed in US, Europe and Japan); and
T-SPOT.TB, a form of ELISPOT (licensed in Europe).

Chest photofluorography has been used in the past for mass screening for tuberculosis.

Treatment


Treatment for TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which makes many antibiotics ineffective and hinders the entry of drugs. The two antibiotics most commonly used are rifampicin and isoniazid. However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 24 months) to entirely eliminate mycobacteria from the body. Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are treated to prevent them from progressing to active TB disease later in life.

Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB (XDR-TB) is also resistant to three or more of the six classes of second-line drugs. The DOTS (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO was based on clinical trials done in the 1970s by Tuberculosis Research Centre, Chennai, India. The country in which a person with TB lives can determine what treatment they receive. This is because multidrug-resistant tuberculosis is resistant to most first-line medications, the use second-line antituberculosis medications is necessary to cure the patient. However, the price of these medications is high; thus poor people in the developing world have no or limited access to these treatments.

Prognosis

Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and begin to multiply. In primary TB disease—1-5% of cases—this occurs soon after infection. However, in the majority of cases, a latent infection occurs that has no obvious symptoms The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.

Epidemiology

Roughly a third of the world's population has been infected with M. tuberculosis, and new infections occur at a rate of one per second. However, not all infections with M. tuberculosis cause TB disease and many infections are asymptomatic. Centers for Disease Control. Fact Sheet: Tuberculosis in the United States. 17 March 2005, Retrieved on 6 October 2006. In 2007, an estimated 13.7 million people had active TB disease, with 9.3 million new cases and 1.8 million deaths; the annual incidence rate varied from 363 per 100,000 in Africa to 32 per 100,000 in the Americas. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs.

In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases. . In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were 30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007.

The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults. World Health Organization (WHO). Global Tuberculosis Control Report, 2006 - Annex 1 Profiles of high-burden countries. (PDF) Retrieved on 13 October 2006. However, in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older people, or of the immunocompromised Centers for Disease Control and Prevention (CDC). 2005 Surveillance Slide Set. (12 September 2006) Retrieved on 13 October 2006. .

There are a number of known factors that make people more susceptible to TB infection: worldwide the most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high incidence of HIV in these countries. World Health Organization (WHO). Global tuberculosis control - surveillance, planning, financing WHO Report 2006. Retrieved on 13 October 2006. Smoking more than 20 cigarettes a day also increases the risk of TB by two to four times. Other disease states that increase the risk of developing tuberculosis are Hodgkin lymphoma, end-stage renal disease, chronic lung disease, malnutrition, and alcoholism.

Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian Hindu Asians were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslims who ate meat and fish daily. this increased risk could be caused by micronutrient deficiencies: possibly iron, vitamin B12 or vitamin D. Globally, the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the immune system. Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty.

History

Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 18,000 years before the present.

. Pictured: Egyptian mummy in the British Museum
Skeletal remains from a Neolithic Settlement in the Eastern Mediterranean show prehistoric humans (7000 BC) had TB, and tubercular decay has been found in the spines of mummies from 3000-2400 BC. Phthisis is a Greek term for tuberculosis; around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal. In South America, the earliest evidence of tuberculosis is associated with the Paracas-Caverna culture (circa 750 BC to circa 100 AD).

Other names

In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and phthisis pulmonalis ; scrofula (in adults), affecting the lymphatic system and resulting in swollen neck glands; tabes mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease, or gibbus of the spine and joints.


Miliary tuberculosis —now commonly known as disseminated TB—occurs when the infection invades the circulatory system, resulting in millet-like seeding of TB bacilli in the lungs as seen on an X-ray. TB is also called Koch's disease, after the scientist Robert Koch.

Folklore

Before the Industrial Revolution, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin, extremely low body heat, a weak heart and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood. Another folk belief told that the affected individual was being forced, nightly, to attend fairy revels, so that the victim wasted away owing to lack of rest; this belief was most common when a strong connection was seen between the fairies and the dead. Katharine Briggs, Consumption, An Encyclopedia of Fairies, Pantheon Books, 1976, p. 80. ISBN 0-394-73467-X Similarly, but less commonly, it was attributed to the victims being hagridden —being transformed into horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest. In the early 20th century, some believed TB to be caused by masturbation.

Study and treatment

The study of tuberculosis, sometimes known as phthisiatry, dates back to The Canon of Medicine written by Ibn Sina (Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease, the first to recognise the association with diabetes, and the first to suggest that it could spread through contact with soil and water. Y. A. Al-Sharrah (2003), The Arab Tradition of Medical Education and its Relationship with the European Tradition, Prospects 33 (4), Springer. George Sarton, Introduction to the History of Science .
(cf. Dr. A. Zahoor and Dr. Z. Haq (1997). Quotations From Famous Historians of Science, Cyberistan.)
He developed the method of quarantine in order to limit the spread of tuberculosis. In ancient times, treatments focused on sufferers' diets. Pliny the Elder described several methods in his Natural History : wolf's liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken in broth .

Although it was established that the pulmonary form was associated with tubercles by Dr Richard Morton in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named tuberculosis until 1839 by J. L. Schönlein. Zur Pathogenie der Impetigines. Auszug aus einer brieflichen Mitteilung an den Herausgeber. Archiv für Anatomie, Physiologie und wissenschaftliche Medicin . 1839, page 82. During the years 1838 – 1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air; they died within a year. Kentucky: Mammoth Cave long on history. CNN . 27 February 2004. Accessed 8 October 2006. The first TB sanatorium opened in 1854 in Görbersdorf, Germany (today Sokołowsko, Poland) by Hermann Brehmer.

The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Nobel Foundation. The Nobel Prize in Physiology or Medicine 1905. Accessed 7 October 2006. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a remedy for tuberculosis in 1890, calling it tuberculin . It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis.

The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called BCG ( Bacillus of Calmette and Guérin). The BCG vaccine was first used on humans in 1921 in France, but it was not until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany.

Tuberculosis, or consumption as it was commonly known, caused the most widespread public concern in the 19th and early 20th centuries as an endemic disease of the urban poor. After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention. Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).

The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907 – 1908 to help the National Tuberculosis Association (later called the American Lung Association).

In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons.

In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics. The disease remained such a significant threat to public health, that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research. Medical Research Council (UK). MRC's contribution to Tuberculosis research. Accessed 2 July 2007.

It was not until 1946 with the development of the antibiotic streptomycin that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax or plombage technique — collapsing an infected lung to rest it and allow lesions to heal — a technique that was of little benefit and was mostly discontinued by the 1950s.

Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005. The number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000 TB patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid).

The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993. World Health Organization (WHO). Frequently asked questions about TB and HIV. Retrieved 6 October 2006. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.

Evolution

Tuberculosis has co-evolved with humans for many thousands of years, and perhaps for several million years. During this evolution, M. tuberculosis has lost numerous coding and non-coding regions in its genome, losses that can be used to distinguish between strains of the bacteria. The implication is that M. tuberculosis strains differ geographically, so their genetic differences can be used to track the origins and movement of each strain.

Society and culture

Through its affecting important historical figures, tuberculosis has influenced particularly European history, and become a theme in art - mostly literature, music, and film.

Public health

Tuberculosis is one of the three primary diseases of poverty along with AIDS and malaria. The Global Fund to Fight AIDS, Tuberculosis and Malaria was started in 2002 to raise finances to address these infectious diseases. Globalization has led to increased opportunities for disease spread. A tuberculosis scare occurred in 2007 when Andrew Speaker flew on a transatlantic flight infected with multi-drug-resistant tuberculosis.

In the United States, the National Center for HIV, STD, and TB Prevention, as part of the Center for Disease Control and Prevention (CDC), is responsible for public health surveillance and prevention research.

Notable victims

Research

The Mycobacterium Tuberculosis Structural Genomics Consortium is a global consortium of scientists conducting research regarding the diagnosis and treatment of tuberculosis. They are attempting to determine the 3-dimensional structures of proteins from M. Tuberculosis .

In other animals


Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers.

Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand is underway. It has been found that herd infection is more likely in areas where infected natural reservoir such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders. Controlling the vectors through possum eradication and monitoring the level of disease in livestock herds through regular surveillance are seen as a two-pronged approach to ridding New Zealand of the disease.

In the Republic of Ireland and the United Kingdom, badgers have been identified as one vector species for the transmission of bovine tuberculosis. As a result, governments have come under pressure from some quarters, primarily dairy farmers, to mount an active campaign of eradication of badgers in certain areas with the purpose of reducing the incidence of bovine TB. The effectiveness of culling on the incidence of TB in cattle is a contentious issue, with proponents and opponents citing their own studies to support their position. Cassidy, Martin. Badgers targeted over bovine TB. BBC News 2 December 2004. Retrieved on 8 May 2006.

References for tuberculosis

Further reading


A nonfiction account of treating TB in Haiti, Peru, Russia, and elsewhere.
. First published in the United Kingdom as Tuberculosis: The Greatest Story Never Told .

External links


General information, public health websites and epidemiology
World Health Organization (WHO) - Tuberculosis

The Stop TB Partnership - established in 2000 with the goal of eliminating tuberculosis as a public health problem

Central Asia Health Review (CAHR). High Prevalence of Multi-Drug Resistant Tuberculosis in Uzbekistan
Tuberculosis on the CDC website
Tuberculosis information from the Health Protection Agency in the UK
Kaiser Family Foundation. Tuberculosis. Globalhealthfacts.org.
United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical Assistance (TBCTA).
Tuberculosis and HIV: HIV InSite Knowledge Base chapter and related resources .

Patient information on tuberculosis
Tuberculosis on Medicinenet.com (HON code compliant)
(CDC) - Questions and Answers About TB, 2007
The Nobel Prize Website. Tuberculosis Educational Game

Professional information and scientific research
Tuberculosis Database is an integrated platform for tuberculosis research, hosting genomic and gene expression data for Mycobacterium tuberculosis and other related species.
Mycobacterium tuberculosis in the BioHealthBase (TB genomics and proteomics database)
Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated August 2003.
Tuberculosis 2007 - a textbook that focuses on research, diagnosis and treatment of tuberculosis
Tuberculosis: A Persistent Threat to Global Health on-line lecture by John McKinney
Sir John Crofton - Daily Telegraph obituary


Tuberculosis



ENTERITIS


In medicine, enteritis refers to inflammation of the small intestine. It is most commonly caused by the ingestion of substances contaminated with pathogenic microorganisms. Dugdale, David C., III, and George F Longstreth., such as Serratia Enteritis . MedlinePlus Medical Encyclopedia, 18 October 2008. Accessed 24 August 2009. Symptoms include abdominal pain, cramping, diarrhea, dehydration and fever. See also inflammation of related organs of the gastrointestinal system: gastritis (stomach), gastroenteritis (stomach and small intestine), colitis (large intestine), and enterocolitis (large and small intestine).

See also

Enteropathy
Gastroenteritis

References



FOODBORNE ILLNESS


Foodborne illness (also foodborne disease and colloquially referred to as food poisoning) is any illness resulting from the consumption of contaminated food.

There are two types of food poisoning: toxic agent and infectious agent. Food infection refers to the presence of bacteria or other microbes which infect the body after consumption. Food intoxication refers to the ingestion of toxins contained within the food, including bacterially produced exotoxins, which can happen even when the microbe that produced the toxin is no longer present or able to cause infection. In spite of the common term food poisoning, most cases are caused by a variety of pathogenic bacteria, viruses, prions or parasites that contaminate food, rather than chemical or natural toxins.

Causes


Foodborne illness usually arises from improper handling, preparation, or food storage. Good hygiene practices before, during, and after food preparation can reduce the chances of contracting an illness. There is a general consensus in the public health community that regular hand-washing is one of the most effective defenses against the spread of foodborne illness. The action of monitoring food to ensure that it will not cause foodborne illness is known as food safety. Foodborne disease can also be caused by a large variety of toxins that affect the environment. For foodborne illness caused by chemicals, see Food contaminants.

Foodborne illness can also be caused by pesticides or medicines in food and naturally toxic substances like poisonous mushrooms or reef fish.

Symptoms and mortality

Symptoms typically begin several hours to several days after consumption and depending on the agent involved, can include one or more of the following: nausea, abdominal pain, vomiting, diarrhea, gastroenteritis, fever, headache or fatigue.

In most cases the body is able to permanently recover after a short period of acute discomfort and illness. However, foodborne illness can result in permanent health problems or even death, especially for people at high risk, including babies, young children, pregnant women (and their fetuses), elderly people, sick people and others with weak immune systems.

Foodborne illness due to campylobacter, yersinia, salmonella or shigella infection is a major cause of reactive arthritis, which typically occurs 1-3 weeks after diarrheal illness. Similarly, people with liver disease are especially susceptible to infections from Vibrio vulnificus, which can be found in oysters or crabs.

Tetrodotoxin poisoning from reef fish and other animals manifests rapidly as numbness and shortness of breath, and is often fatal.

Incubation period

The delay between consumption of a contaminated food and appearance of the first symptoms of illness is called the incubation period. This ranges from hours to days (and rarely months or even years, such as in the case of Listeriosis or Creutzfeldt-Jacob disease), depending on the agent, and on how much was consumed. If symptoms occur within 1-6 hours after eating the food, it suggests that it is caused by a bacterial toxin or a chemical rather than live bacteria.

The long incubation period of many foodborne illnesses tends to cause sufferers to attribute their symptoms to stomach flu .

During the incubation period, microbes pass through the stomach into the intestine, attach to the cells lining the intestinal walls, and begin to multiply there. Some types of microbes stay in the intestine, some produce a toxin that is absorbed into the bloodstream, and some can directly invade the deeper body tissues. The symptoms produced depend on the type of microbe.

Infectious dose

The infectious dose is the amount of agent that must be consumed to give rise to symptoms of foodborne illness, and varies according to the agent and the consumer's age and overall health. In the case of Salmonella a relatively large inoculum of 1 million to 1 billion organisms is necessary to produce symptoms in healthy human volunteers , as Salmonellae are very sensitive to acid. An unusually high stomach pH level (low acidity) greatly reduces the number of bacteria required to cause symptoms by a factor of between 10 and 100.

Pathogenic agents

Bacteria

Bacteria are a common cause of foodborne illness. In the United Kingdom during 2000 the individual bacteria involved were as follows: Campylobacter jejuni 77.3%, Salmonella 20.9%, 1.4%, and all others less than 0.1%. In the past, bacterial infections were thought to be more prevalent because few places had the capability to test for norovirus and no active surveillance was being done for this particular agent. Symptoms for bacterial infections are delayed because the bacteria need time to multiply. They are usually not seen until 12-72 hours or more after eating contaminated food.

Most common bacterial foodborne pathogens are:
Campylobacter jejuni which can lead to secondary Guillain-Barré syndrome and periodontitis
Clostridium perfringens, the cafeteria germ
Salmonella spp. - its S. typhimurium infection is caused by consumption of eggs that are not adequately cooked or by other interactive human-animal pathogens
enterohemorrhagic (EHEC) which causes hemolytic-uremic syndrome

Other common bacterial foodborne pathogens are:
Bacillus cereus
Escherichia coli, other virulence properties, such as enteroinvasive (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroaggregative (EAEC or EAgEC)
Listeria monocytogenes
Shigella spp.
Staphylococcus aureus
Streptococcus
Vibrio cholerae, including O1 and non-O1
Vibrio parahaemolyticus
Vibrio vulnificus
Yersinia enterocolitica and Yersinia pseudotuberculosis

Less common bacterial agents:
Brucella spp.
Corynebacterium ulcerans
Coxiella burnetii or Q fever
Plesiomonas shigelloides

Exotoxins

In addition to disease caused by direct bacterial infection, some foodborne illnesses are caused by exotoxins which are excreted by the cell as the bacterium grows. Exotoxins can produce illness even when the microbes that produced them have been killed. Symptoms typically appear after 1-6 hours depending on the amount of toxin ingested.

Clostridium botulinum
Clostridium perfringens
Staphylococcus aureus
Bacillus cereus

For example Staphylococcus aureus produces a toxin that causes intense vomiting. The rare but potentially deadly disease botulism occurs when the anaerobic bacterium Clostridium botulinum grows in improperly canned low-acid foods and produces botulin, a powerful paralytic toxin.

Pseudoalteromonas tetraodonis, certain species of Pseudomonas and Vibrio, and some other bacteria, produce the lethal tetrodotoxin, which is present in the tissues of some living animal species rather than being a product of decomposition.

Mycotoxins and alimentary mycotoxicoses

The term alimentary mycotoxicoses refers to the effect of poisoning by Mycotoxins through food consumption. Mycotoxins have prominently affected on human and animal health such as an outbreak which occurred in the UK in 1960 that caused the death of 100,000 turkeys which had consumed aflatoxin-contaminated peanut meal and the death of 5000 human lives by Alimentary toxic aleukia (ALA) in the USSR in World War II. The common foodborne Mycotoxins include:
Aflatoxins - originated from Aspergillus parasiticus and Aspergillus flavus. They are frequently found in tree nuts, peanuts, maize, sorghum and other oilseeds, including corn and cottonseeds. The pronounced forms of Aflatoxins are those of B1, B2, G1, and G2, amongst which Aflatoxin B1 predominantly targets the liver, which will result in necrosis, cirrhosis, and carcinoma. The official document can be found at FDA's website.
Altertoxins - are those of Alternariol (AOH), Alternariol methyl ether (AME), Altenuene (ALT), Altertoxin-1 (ATX-1), Tenuazonic acid (TeA) and Radicinin (RAD), originated from Alternaria spp. Some of the toxins can be present in sorghum, ragi, wheat and tomatoes.
Citrinin
Citreoviridin
Cyclopiazonic acid
Cytochalasins
Ergot alkaloids / Ergopeptine alkaloids - Ergotamine
Fumonisins - Crop corn can be easily contaminated by the fungi Fusarium moniliforme, and its Fumonisin B1 will cause Leukoencephalomalacia (LEM) in horses, Pulmonary edema syndrome (PES) in pigs, liver cancer in rats and Esophageal cancer in humans. For human and animal health, both the FDA and the EC have regulated the content levels of toxins in food and animal feed.
Fusaric acid
Fusarochromanone
Kojic acid
Lolitrem alkaloids
Moniliformin
3-Nitropropionic acid
Nivalenol
Ochratoxins - In Australia, The Limit of Reporting (LOR) level for Ochratoxin A (OTA) analyses in 20th Australian Total Diet Survey was 1 µg/kg, whereas the EC restricts the content of OTA to 5 µg/kg in cereal commodities, 3 µg/kg in processed products and 10 µg/kg in dried vine fruits.
Oosporeine
Patulin - Currently, this toxin has been advisably regulated on fruit products. The EC and the FDA have limited it to under 50 µg/kg for fruit juice and fruit nectar, while limits of 25 µg/kg for solid-contained fruit products and 10 µg/kg for baby foods were specified by the EC.
Phomopsins
Sporidesmin A
Sterigmatocystin
Tremorgenic mycotoxins - Five of them have been reported to be associated with molds found in fermented meats. These are Fumitremorgen B, Paxilline, Penitrem A, Verrucosidin, and Verruculogen.
Trichothecenes - sourced from Cephalosporium, Fusarium, Myrothecium, Stachybotrys and Trichoderma. The toxins are usually found in molded maize, wheat, corn, peanuts and rice, or animal feed of hay and straw. Four trichothecenes, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) have been most commonly encountered by humans and animals. The consequences of oral intake of, or dermal exposure to, the toxins will result in Alimentary toxic aleukia, neutropenia, aplastic anemia, thrombocytopenia and/or skin irritation. In 1993, the FDA issued a document for the content limits of DON in food and animal feed at an advisory level.
Zearalenone
Zearalenols

Emerging foodborne pathogens

Many foodborne illnesses remain poorly understood. Approximately sixty percent of outbreaks are caused by unknown sources.

Aeromonas hydrophila, Aeromonas caviae, Aeromonas sobria

Preventing bacterial food poisoning

Proper storage and refrigeration of food help in the prevention of food poisoning
Prevention is mainly the role of the state, through the definition of strict rules of hygiene and a public services of veterinary surveying of animal products in the food chain, from farming to the transformation industry and delivery (shops and restaurants). This regulation includes:
traceability: in a final product, it must be possible to know the origin of the ingredients (originating farm, identification of the harvesting or of the animal) and where and when it was processed; the origin of the illness can thus be tracked and solved (and possibly penalized), and the final products can be removed from the sale if a problem is detected;
enforcement of hygiene procedures like HACCP and the cold chain ;
power of control and of law enforcement of veterinarians.

In August 2006, the United States Food and Drug Administration approved Phage therapy which involves spraying meat with viruses that infect bacteria, and thus preventing infection. This has raised concerns, because without mandatory labelling consumers wouldn't be aware that meat and poultry products have been treated with the spray.

At home, prevention mainly consists of good food safety practices. Many forms of bacterial poisoning can be prevented even if food is contaminated by cooking it sufficiently, and either eating it quickly or refrigerating it effectively . Many toxins, however, are not destroyed by heat treatment.

Viruses

Viral infections make up perhaps one third of cases of food poisoning in developed countries. In the US, more than 50% of cases are viral and noroviruses are the most common foodborne illness, causing 57% of outbreaks in 2004. Foodborne viral infection are usually of intermediate (1-3 days) incubation period, causing illnesses which are self-limited in otherwise healthy individuals, and are similar to the bacterial forms described above.
Enterovirus
Hepatitis A is distinguished from other viral causes by its prolonged (2-6 week) incubation period and its ability to spread beyond the stomach and intestines, into the liver. It often induces jaundice, or yellowing of the skin, and rarely leads to chronic liver dysfunction. The virus has been found to cause the infection due to the consumption of fresh-cut produce which has fecal contamination.
Hepatitis E
Norovirus
Rotavirus

Parasites

Most foodborne parasites are zoonoses.

Platyhelminthes:
Diphyllobothrium sp.
Nanophyetus sp.
Taenia saginata
Taenia solium
Fasciola hepatica
: See also: Tapeworm and Flatworm
Nematode:
Anisakis sp.
Ascaris lumbricoides
Eustrongylides sp.
Trichinella spiralis
Trichuris trichiura
Protozoa:
Acanthamoeba and other free-living amoebae
Cryptosporidium parvum
Cyclospora cayetanensis
Entamoeba histolytica
Giardia lamblia
Sarcocystis hominis
Sarcocystis suihominis
Toxoplasma gondii

Natural toxins

Several foods can naturally contain toxins, many of which are not produced by bacteria. Plants in particular may be toxic; animals which are naturally poisonous to eat are rare. In evolutionary terms, animals can escape being eaten by fleeing; plants can use only passive defenses such as poisons and distasteful substances, for example capsaicin in chili peppers and pungent sulfur compounds in garlic and onions. Most animal poisons are not synthesised by the animal, but acquired by eating poisonous plants to which the animal is immune, or by bacterial action.
Alkaloids
Ciguatera poisoning
Grayanotoxin (honey intoxication)
Mushroom toxins
Phytohaemagglutinin (red kidney bean poisoning; destroyed by boiling)
Pyrrolizidine alkaloids
Shellfish toxin, including paralytic shellfish poisoning, diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning and ciguatera fish poisoning
Scombrotoxin
Tetrodotoxin (fugu fish poisoning)

Some plants contain substances which are toxic in large doses, but have therapeutic properties in appropriate dosages.
Foxglove contains cardiac glycosides.
Poisonous hemlock (conium) has medicinal uses.

Other pathogenic agents

Prions, resulting in Creutzfeldt-Jakob disease

Ptomaine poisoning

An early theory on the causes of food poisoning involved ptomaines (from Greek ptōma, fall, fallen body, corpse ), alkaloids found in decaying animal and vegetable matter. While some alkaloids do cause poisoning, the discovery of bacteria left the ptomaine theory obsolete and the word ptomaine is no longer used scientifically.

Global Impact

In modern times, rapid globalization of food production and trade has increased the potential likelihood of food contamination. Many outbreaks of foodborne diseases that were once contained within a small community may now take place on global dimensions. Food safety authorities all over the world have acknowledged that ensuring food safety must not only be tackled at the national level but also through closer linkages among food safety authorities at the international level. This is important for exchanging routine information on food safety issues and to have rapid access to information in case of food safety emergencies.

It is difficult to estimate the global incidence of foodborne disease, but it has been reported that in the year 2000 about 2.1 million people died from diarrhoeal diseases. Many of these cases have been attributed to contamination of food and drinking water. Additionally, diarrhoea is a major cause of malnutrition in infants and young children.

Even in industrialized countries, up to 30% of the population of people have been reported to suffer from foodborne diseases every year. In the U.S, around 76 million cases of foodborne diseases, which resulted in 325,000 hospitalizations and 5,000 deaths, are estimated to occur each year. Developing countries in particular, are worst affected by foodborne illnesses due to the presence of a wide range of diseases, including those caused by parasites. Foodborne illnesses can and did inflict serious and extensive harm on society. In 1994, an outbreak of salmonellosis due to contaminated ice cream occurred in the USA, affecting an estimated 224,000 persons. In 1988, an outbreak of hepatitis A, resulting from the consumption of contaminated clams, affected some 300,000 individuals in China.

Food contamination creates an enormous social and economic strain on societies. In the U.S., diseases caused by the major pathogens alone are estimated to cost up to US $35 billion annually (1997) in medical costs and lost productivity. The re-emergence of cholera in Peru in 1991 resulted in the loss of US $500 million in fish and fishery product exports that year.

Statistics

Every year there are an estimated 76 million foodborne illnesses in the United States (26,000 cases for 100,000 inhabitants), 2 million in the United Kingdom (3,400 cases for 100,000 inhabitants) and 750,000 in France (1,210 cases for 100,000 inhabitants).

United States

In the United States, using FoodNet data from 1996-1998, the CDCP estimated there were 76 million foodborne illnesses (26,000 cases for 100,000 inhabitants): -->
325,000 were hospitalized (111 per 100,000 inhabitants);
5,000 people died (1.7 per 100,000 inhabitants.).
Major pathogens from foodborne illness in the United States cost upwards of US $35 billion in medical costs and lost productivity (1997)

France

In France, for 750,000 cases(1,210 per 100,000 inhabitants):
70,000 people consulted in the emergency department of an hospital (113 per 100,000 inhabitants.);
113,000 people were hospitalized (24 per 100,000 inhabitants);
400 people died (0.9 per 100,000 inhabitants).

Australia

In Australia, there are an estimated 5.4 million cases of food-borne illness every year, causing:
18,000 hospitalisations
120 deaths
2.1 million lost days off work
1.2 million doctor consultations
300,000 prescriptions for antibiotics

Outbreaks

The vast majority of reported cases of foodborne illness occur as individual or sporadic cases. The origin of most sporadic cases is undetermined. In the United States, where people eat outside the home frequently, most outbreaks (58%) originate from commercial food facilities (2004 FoodNet data). An outbreak is defined as occurring when two or more people experience similar illness after consuming food from a common source.

Often, a combination of events contributes to an outbreak, for example, food might be left at room temperature for many hours, allowing bacteria to multiply which is compounded by inadequate cooking which results in a failure to kill the dangerously elevated bacterial levels.

Outbreaks are usually identified when those affected know each other. However, more and more, outbreaks are identified by public health staff from unexpected increases in laboratory results for certain strains of bacteria. Outbreak detection and investigation in the United States is primarily handled by local health jurisdictions and is inconsistent from district to district. It is estimated that 1-2% of outbreaks are detected.

Political issues

United Kingdom

In postwar Aberdeen (1964) a large scale (>400 cases) outbreak of Typhoid occurred, this was caused by contaminated corned beef which had been imported from Argentina The corned beef was placed in cans and because the cooling plant had failed, cold river water from the Plate estuary was used to cool the cans. One of the cans had a defect and the meat inside was contaminated. This meat was then sliced using a meat slicer in a shop in Aberdeen, and a lack of cleaning the machinery lead to spreading the contamination to other meats cut in the slicer. These meats were then eaten by the people of Aberdeen who then became ill.

In the UK serious outbreaks of food-borne illness since the 1970s prompted key changes in UK food safety law. These included the death of 19 patients in the Stanley Royd Hospital outbreak and the bovine spongiform encephalopathy (BSE, mad cow disease) outbreak identified in the 1980s. The death of 17 people in the 1996 Wishaw outbreak of E. coli O157 was a precursor to the establishment of the Food Standards Agency which, according to Tony Blair in the 1998 white paper A Force for Change Cm 3830 would be powerful, open and dedicated to the interests of consumers .

United States

In 2001, the Center for Science in the Public Interest (CSPI) petitioned the United States Department of Agriculture to require meat packers to remove spinal cords before processing cattle carcasses for human consumption, a measure designed to lessen the risk of infection by variant Creutzfeldt-Jakob disease. The petition was supported by the American Public Health Association, the Consumer Federation of America, the Government Accountability Project, the National Consumers League, and Safe Tables Our Priority. This was opposed by the National Cattlemen's Beef Association, the National Renderers Association, the National Meat Association, the Pork Producers Council, sheep raisers, milk producers, the Turkey Federation, and eight other organizations from the animal-derived food industry. This was part of a larger controversy regarding the United States' violation of World Health Organization proscriptions to lessen the risk of infection by variant Creutzfeldt-Jakob disease.

None of the US Department of Health and Human Services targets

Organizations

;World Health Organization Food Safety Department
:The WHO provides scientific advice for organizations and the public on issues concerning the safety of food. It serves as a medium linking the food safety systems in countries around the world. Food safety is currently one of WHO's top ten priorities. Food Safety is one of the major issues in our world today, and the Organization calls for more systematic and aggressive steps to be taken to significantly reduce the risk of foodborne diseases.
;The Department of Food Safety, Zoonoses and Foodborne Diseases
:The Department of Food Safety, Zoonoses and Foodborne Diseases is a department under the WHO. Its mission is to: to reduce the serious negative impact of foodborne diseases worldwide. According to the WHO website, food and waterborne diarrhoeal diseases are leading causes of illness and death in less developed countries, killing approximately 3.8 million people annually, most of whom are children.
;The International Food Safety Authorities Network (INFOSAN)
:This network is intended to complement and support the existing WHO Global Outbreak Alert and Response Network (GOARN) which includes a Chemical Alert and Response component.

Academic resources

Periodicals

International Journal of Food Microbiology, ISSN: 0168-1605, Elsevier
Foodborne Pathogens and Disease, ISSN: 1535-3141, Mary Ann Liebert, Inc.
Mycopathologia, ISSN: 1573-0832 (electronic) 0301-486X (paper), Springer

Books

Advances in Food Mycology (Advances in Experimental Medicine and Biology) (2006) by A.D. Hocking et al., ISBN 978-0387283913 (electronic) 978-0387283852 (paper), Springer
Foodborne Infections and Intoxications (2006) by Hans P. Riemann and Dean O. Cliver, ISBN 012588365X, Elsevier
Foodborne Pathogens: Microbiology And Molecular Biology (2005) by Pina M. Fratamico et al., ISBN 190445500X ISBN 978-1904455004, Caister Academic Press

See also


List of foodborne illness outbreaks by country
1984 Rajneeshee bioterror attack
2006 North American E. coli outbreak
Alexander Litvinenko poisoning
Attack rate
United States Disease Control and Prevention
Food allergy
Food hygiene
Food quality
Food Microbiology
Food safety
Food Testing Strips
Gastroenteritis
Juice
List of infectious diseases
List of poisonings
Mycotoxicology
Minamata disease
Munir Said Thalib
Refrigerate after opening
Risk assessment
Zoonotic pathogens

References

External links


Top 10 Food Poisoning Risks, New York Times . October 6, 2009.
Surveillance for Foodborne-Disease Outbreaks --- United States, 1998--2002
Foodborne diseases, emerging, WHO, Fact sheet N°124, revised January 2002
Foodborne illness information pages, NSW Food Authority
Food safety and foodborne illness, WHO, Fact sheet N°237, revised January 2002
UK Health protection Agency
US PulseNet
Food poisoning from NHS Direct Online
Food Safety Network hosted at the University of Guelph, Canada.
Food Standard Agency website
Australian OzFoodnet Foodborne Diseases Surveillance Network




TUBERCULOUS MENINGITIS


Tuberculous meningitis is also known as TB meningitis or tubercular meningitis.

Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelops the central nervous system. It is the most common form of CNS tuberculosis.

Clinical features

Fever and headache are the cardinal features. Confusion is a late feature and coma bears a poor prognosis. Meningism is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.

Pathology

Mycobacterium tuberculosis of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain. When the inflammation is in the brain stem subarachnoid area, cranial nerve roots may be affected. The symptoms will mimic those of space-occupying lesions. Infection begins in the lungs and may spread to the meninges by a variety of routes.

Blood-borne spread certainly occurs and 25% of patients with miliary TB have TB meningitis, presumably by crossing the blood-brain barrier ; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain (a so-called Rich focus); an even smaller proportion get it from rupture of a bony focus in the spine. It is rare and unusual for TB of the spine to cause TB of the central nervous system, but isolated cases have been described.

Diagnosis

Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1 ml of fluid should be taken (preferably 5 to 10ml).

The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding.

ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative,

More than half of cases of TB meningitis cannot be confirmed microbiologically, and these patients are treated on the basis of clinical suspicion only. The culture of TB from CSF takes a minimum of two weeks, and therefore the majority of patients with TB meningitis are started on treatment before the diagnosis is confirmed.

Nucleic acid amplification tests (NAAT)

This is a heterogeneous group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that for diagnosing tuberculous meningitis Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%) . In the NHS meta-analysis, they found the pooled prevalence of TB meningitis to be 29% ; however there was much heterogeneity in the reported sensitivities. Using a clinical calculator, these numbers yield a positive predictive value of 94% and a negative predictive value of 90%; however the 30% prevalence may be high due to referral bias. Alternate estimates of disease prevalence can be entered into the clinical calculator to refine the predictive values.These intcances vary from patient to patient according to their pathology.

Imaging

Imaging studies such as CT or MRI may show features strongly suggestive of TB meningitis, but cannot diagnose it.

Treatment

See: tuberculosis treatment

The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids are always used in the first six weeks of treatment (and sometimes for longer). A few patients may require immunomodulatory agents such as thalidomide.

Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis.

Hydrocephalus occurs as a complication in about a third of patients with TB meningitis and will require a ventricular shunt.

References



TUBERCULOUS GUMMA

Tuberculous gumma (also known as a Metastatic tuberculous abscess, and Metastatic tuberculous ulcer ) is a cutaneous condition characterized histologically by massive necrosis. Restated, this is a skin condition that results from hematogenous dissemination of mycobacteria from a primary focus, resulting in firm, nontender erythematous nodules that soften, ulcerate, and form sinuses.

See also

Tuberculosis verrucosa cutis
Tuberculosis cutis orificialis
List of cutaneous conditions

References



TUBERCULOUS LYMPHADENITIS

Tuberculous lymphadenitis is a chronic specific granulomatous inflammation with caseation necrosis of the lymph node.

The characteristic morphological element is the tuberculous granuloma (caseating tubercule): giant multinucleated cells (Langhans cells), surrounded by epithelioid cells aggregates, T cell lymphocytes and few fibroblasts. Granulomatous tubercules evolve to central caseous necrosis and tend to become confluent, replacing the lymphoid tissue.

External links

Microscopy



TUBERCULOUS PERICARDITIS


Tuberculous pericarditis is a form of pericarditis.

Pericarditis caused by tuberculosis is difficult to diagnose, because definitive diagnosis requires culturing Mycobacterium tuberculosis from aspirated pericardial fluid or pericardial biopsy, which requires high technical skill and is often not diagnostic (the yield from culture is low even with optimum specimens). The Tygerberg scoring system helps the clinician to decide whether pericarditis is due to tuberculosis or whether it is due to another cause: night sweats (1 point), weight loss (1 point), fever (2 point), serum globulin > 40g/l (3 points), blood total leucocyte count <10 x 10 9 /l (3 points); a total score of 6 or more is highly suggestive of tuberculous pericarditis. Pericardial fluid with an interferon-γ level greater than 50 pg/ml is highly specific for tuberculous pericarditis.

References



TUBERCULOUS CELLULITIS

Tuberculous cellulitis is a skin condition resulting from infection with mycobacterium, and presenting as cellulitis.

See also

Lupus vulgaris
Metastatic tuberculous abscess or ulceration
Miliary tuberculosis
Skin lesion

References



FOODBORNE DISEASE

Foodborne illness



BACTERIA

The bacteria ( ; singular : bacterium) are a large group of unicellular, prokaryote, microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals. Bacteria are ubiquitous in every habitat on Earth, growing in soil, acidic hot springs, radioactive waste, water, and deep in the Earth's crust, as well as in organic matter and the live bodies of plants and animals. There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water; in all, there are approximately five nonillion (5×10 30 ) bacteria on Earth, forming much of the world's biomass. Bacteria are vital in recycling nutrients, with many steps in nutrient cycles depending on these organisms, such as the fixation of nitrogen from the atmosphere and putrefaction. However, most bacteria have not been characterized, and only about half of the phyla of bacteria have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.

There are approximately ten times as many bacterial cells in the human flora of bacteria as there are human cells in the body, with large numbers of bacteria on the skin and as gut flora. The vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, and a few are beneficial. However, a few species of bacteria are pathogenic and cause infectious diseases, including cholera, syphilis, anthrax, leprosy and bubonic plague. The most common fatal bacterial diseases are respiratory infections, with tuberculosis alone killing about 2 million people a year, mostly in sub-Saharan Africa. In developed countries, antibiotics are used to treat bacterial infections and in agriculture, so antibiotic resistance is becoming common. In industry, bacteria are important in sewage treatment, the production of cheese and yoghurt through fermentation, as well as in biotechnology, and the manufacture of antibiotics and other chemicals.

Once regarded as plants constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and rarely harbour membrane-bound organelles. Although the term bacteria traditionally included all prokaryotes, the scientific classification changed after the discovery in the 1990s that prokaryotes consist of two very different groups of organisms that evolved independently from an ancient common ancestor. These evolutionary domains are called Bacteria and Archaea.

History of bacteriology

Antonie van Leeuwenhoek, the first microbiologist and the first person to observe bacteria using a microscope.

Bacteria were first observed by Antonie van Leeuwenhoek in 1676, using a single-lens microscope of his own design. He called them animalcules and published his observations in a series of letters to the Royal Society. The name bacterium was introduced much later, by Christian Gottfried Ehrenberg in 1838.

Louis Pasteur demonstrated in 1859 that the fermentation process is caused by the growth of microorganisms, and that this growth is not due to spontaneous generation. (Yeasts and molds, commonly associated with fermentation, are not bacteria, but rather fungi.) Along with his contemporary, Robert Koch, Pasteur was an early advocate of the germ theory of disease.
Robert Koch was a pioneer in medical microbiology and worked on cholera, anthrax and tuberculosis. In his research into tuberculosis, Koch finally proved the germ theory, for which he was awarded a Nobel Prize in 1905. In Koch's postulates, he set out criteria to test if an organism is the cause of a disease; these postulates are still used today.

Though it was known in the nineteenth century that bacteria are the cause of many diseases, no effective antibacterial treatments were available. In 1910, Paul Ehrlich developed the first antibiotic, by changing dyes that selectively stained Treponema pallidum —the spirochaete that causes syphilis—into compounds that selectively killed the pathogen. Ehrlich had been awarded a 1908 Nobel Prize for his work on immunology, and pioneered the use of stains to detect and identify bacteria, with his work being the basis of the Gram stain and the Ziehl-Neelsen stain.

A major step forward in the study of bacteria was the recognition in 1977 by Carl Woese that archaea have a separate line of evolutionary descent from bacteria. This new phylogenetic taxonomy was based on the sequencing of 16S ribosomal RNA, and divided prokaryotes into two evolutionary domains, as part of the three-domain system.

Origin and early evolution

The ancestors of modern bacteria were single-celled microorganisms that were the first forms of life to develop on earth, about 4 billion years ago. For about 3 billion years, all organisms were microscopic, and bacteria and archaea were the dominant forms of life. Although bacterial fossils exist, such as stromatolites, their lack of distinctive morphology prevents them from being used to examine the history of bacterial evolution, or to date the time of origin of a particular bacterial species. However, gene sequences can be used to reconstruct the bacterial phylogeny, and these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. The most recent common ancestor of bacteria and archaea was probably a hyperthermophile that lived about 2.5 billion-3.2 billion years ago.

Bacteria were also involved in the second great evolutionary divergence, that of the archaea and eukaryotes. Here, eukaryotes resulted from ancient bacteria entering into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves possibly related to the Archaea. This involved the engulfment by proto-eukaryotic cells of alpha-proteobacterial symbionts to form either mitochondria or hydrogenosomes, which are still found in all known Eukarya (sometimes in highly reduced form, e.g. in ancient amitochondrial protozoa). Later on, some eukaryotes that already contained mitochondria also engulfed cyanobacterial-like organisms. This led to the formation of chloroplasts in algae and plants. There are also some algae that originated from even later endosymbiotic events. Here, eukaryotes engulfed a eukaryotic algae that developed into a second-generation plastid. This is known as secondary endosymbiosis.

Morphology


Bacteria display a wide diversity of shapes and sizes, called morphologies . Bacterial cells are about one tenth the size of eukaryotic cells and are typically 0.5-5.0 micrometres in length. However, a few species-for example Thiomargarita namibiensis and Epulopiscium fishelsoni -are up to half a millimetre long and are visible to the unaided eye. Among the smallest bacteria are members of the genus Mycoplasma, which measure only 0.3 micrometres, as small as the largest viruses. Some bacteria may be even smaller, but these ultramicrobacteria are not well-studied.

Most bacterial species are either spherical, called cocci ( sing . coccus, from Greek kókkos, grain, seed) or rod-shaped, called bacilli ( sing . bacillus, from Latin baculus, stick). Elongation is associated with swimming. Some rod-shaped bacteria, called vibrio, are slightly curved or comma-shaped; others, can be spiral-shaped, called spirilla, or tightly coiled, called spirochaetes. A small number of species even have tetrahedral or cuboidal shapes. This wide variety of shapes is determined by the bacterial cell wall and cytoskeleton, and is important because it can influence the ability of bacteria to acquire nutrients, attach to surfaces, swim through liquids and escape predators.

Many bacterial species exist simply as single cells, others associate in characteristic patterns: Neisseria form diploids (pairs), Streptococcus form chains, and Staphylococcus group together in bunch of grapes clusters. Bacteria can also be elongated to form filaments, for example the Actinobacteria. Filamentous bacteria are often surrounded by a sheath that contains many individual cells. Certain types, such as species of the genus Nocardia, even form complex, branched filaments, similar in appearance to fungal mycelia.

The range of sizes shown by prokaryotes, relative to those of other organisms and biomolecules

Bacteria often attach to surfaces and form dense aggregations called biofilms or bacterial mats. These films can range from a few micrometers in thickness to up to half a meter in depth, and may contain multiple species of bacteria, protists and archaea. Bacteria living in biofilms display a complex arrangement of cells and extracellular components, forming secondary structures such as microcolonies, through which there are networks of channels to enable better diffusion of nutrients. Biofilms are also important in medicine, as these structures are often present during chronic bacterial infections or in infections of implanted medical devices, and bacteria protected within biofilms are much harder to kill than individual isolated bacteria.

Even more complex morphological changes are sometimes possible. For example, when starved of amino acids, Myxobacteria detect surrounding cells in a process known as quorum sensing, migrate towards each other, and aggregate to form fruiting bodies up to 500 micrometres long and containing approximately 100,000 bacterial cells. In these fruiting bodies, the bacteria perform separate tasks; this type of cooperation is a simple type of multicellular organisation. For example, about one in 10 cells migrate to the top of these fruiting bodies and differentiate into a specialised dormant state called myxospores, which are more resistant to drying and other adverse environmental conditions than are ordinary cells.

Cellular structure

Intracellular structures

The bacterial cell is surrounded by a lipid membrane, or cell membrane, which encloses the contents of the cell and acts as a barrier to hold nutrients, proteins and other essential components of the cytoplasm within the cell. As they are prokaryotes, bacteria do not tend to have membrane-bound organelles in their cytoplasm and thus contain few large intracellular structures. They consequently lack a nucleus, mitochondria, chloroplasts and the other organelles present in eukaryotic cells, such as the Golgi apparatus and endoplasmic reticulum. Bacteria were once seen as simple bags of cytoplasm, but elements such as prokaryotic cytoskeleton,

Micro-compartments such as carboxysome provides a further level of organization, which are compartments within bacteria that are surrounded by polyhedral protein shells, rather than by lipid membranes.

Many important biochemical reactions, such as energy generation, occur by concentration gradients across membranes, a potential difference also found in a battery. The general lack of internal membranes in bacteria means reactions such as electron transport occur across the cell membrane between the cytoplasm and the periplasmic space. These light-gathering complexs may even form lipid-enclosed structures called chlorosomes in green sulfur bacteria. Other proteins import nutrients across the cell membrane, or to expel undesired molecules from the cytoplasm.

, below is an image of purified carboxysomes. On the right is a model of their structure. Scale bars are 100 nm.
Bacteria do not have a membrane-bound nucleus, and their genetic material is typically a single circular chromosome located in the cytoplasm in an irregularly shaped body called the nucleoid. The nucleoid contains the chromosome with associated proteins and RNA. The order Planctomycetes are an exception to the general absence of internal membranes in bacteria, because they have a membrane around their nucleoid and contain other membrane-bound cellular structures. Like all living organisms, bacteria contain ribosomes for the production of proteins, but the structure of the bacterial ribosome is different from those of eukaryotes and Archaea.

Some bacteria produce intracellular nutrient storage granules, such as glycogen, polyphosphate, sulfur or polyhydroxyalkanoates. These granules enable bacteria to store compounds for later use. Certain bacterial species, such as the photosynthetic Cyanobacteria, produce internal gas vesicles, which they use to regulate their buoyancy - allowing them to move up or down into water layers with different light intensities and nutrient levels.

Extracellular structures

Around the outside of the cell membrane is the bacterial cell wall. Bacterial cell walls are made of peptidoglycan (called murein in older sources), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Bacterial cell walls are different from the cell walls of plants and fungi, which are made of cellulose and chitin, respectively. The cell wall of bacteria is also distinct from that of Archaea, which do not contain peptidoglycan. The cell wall is essential to the survival of many bacteria, and the antibiotic penicillin is able to kill bacteria by inhibiting a step in the synthesis of peptidoglycan.

There are broadly speaking two different types of cell wall in bacteria, called Gram-positive and Gram-negative. The names originate from the reaction of cells to the Gram stain, a test long-employed for the classification of bacterial species.

Gram-positive bacteria possess a thick cell wall containing many layers of peptidoglycan and teichoic acids. In contrast, Gram-negative bacteria have a relatively thin cell wall consisting of a few layers of peptidoglycan surrounded by a second lipid membrane containing lipopolysaccharides and lipoproteins. Most bacteria have the Gram-negative cell wall, and only the Firmicutes and Actinobacteria (previously known as the low G+C and high G+C Gram-positive bacteria, respectively) have the alternative Gram-positive arrangement. These differences in structure can produce differences in antibiotic susceptibility; for instance, vancomycin can kill only Gram-positive bacteria and is ineffective against Gram-negative pathogens, such as Haemophilus influenzae or Pseudomonas aeruginosa .

In many bacteria an S-layer of rigidly arrayed protein molecules covers the outside of the cell. This layer provides chemical and physical protection for the cell surface and can act as a macromolecular diffusion barrier. S-layers have diverse but mostly poorly understood functions, but are known to act as virulence factors in Campylobacter and contain surface enzymes in Bacillus stearothermophilus .

Flagella are rigid protein structures, about 20  nanometres in diameter and up to 20 micrometres in length, that are used for motility. Flagella are driven by the energy released by the transfer of ions down an electrochemical gradient across the cell membrane.

Fimbriae are fine filaments of protein, just 2-10 nanometres in diameter and up to several micrometers in length. They are distributed over the surface of the cell, and resemble fine hairs when seen under the electron microscope. Fimbriae are believed to be involved in attachment to solid surfaces or to other cells and are essential for the virulence of some bacterial pathogens. Pili ( sing . pilus) are cellular appendages, slightly larger than fimbriae, that can transfer genetic material between bacterial cells in a process called conjugation (see bacterial genetics, below).

Capsules or slime layers are produced by many bacteria to surround their cells, and vary in structural complexity: ranging from a disorganised slime layer of extra-cellular polymer, to a highly structured capsule or glycocalyx. These structures can protect cells from engulfment by eukaryotic cells, such as macrophages.

The assembly of these extracellular structures is dependent on bacterial secretion systems. These transfer proteins from the cytoplasm into the periplasm or into the environment around the cell. Many types of secretion systems are known and these structures are often essential for the virulence of pathogens, so are intensively studied.

Endospores

Bacillus anthracis (stained purple) growing in cerebrospinal fluid

Certain genera of Gram-positive bacteria, such as Bacillus, Clostridium, Sporohalobacter, Anaerobacter and Heliobacterium, can form highly resistant, dormant structures called endospores. In almost all cases, one endospore is formed and this is not a reproductive process, although Anaerobacter can make up to seven endospores in a single cell. Endospores have a central core of cytoplasm containing DNA and ribosomes surrounded by a cortex layer and protected by an impermeable and rigid coat.

Endospores show no detectable metabolism and can survive extreme physical and chemical stresses, such as high levels of UV light, gamma radiation, detergents, disinfectants, heat, pressure and desiccation. and endospores even allow bacteria to survive exposure to the vacuum and radiation in space. Endospore-forming bacteria can also cause disease: for example, anthrax can be contracted by the inhalation of Bacillus anthracis endospores, and contamination of deep puncture wounds with Clostridium tetani endospores causes tetanus.

Metabolism

Bacteria exhibit an extremely wide variety of metabolic types. The distribution of metabolic traits within a group of bacteria has traditionally been used to define their taxonomy, but these traits often do not correspond with modern genetic classifications. Bacterial metabolism is classified into nutritional groups on the basis of three major criteria: the kind of energy used for growth, the source of carbon, and the electron donors used for growth. An additional criterion of respiratory microorganisms are the electron acceptors used for aerobic or anaerobic respiration.

Carbon metabolism in bacteria is either heterotrophic, where organic carbon compounds are used as carbon sources, or autotrophic, meaning that cellular carbon is obtained by fixing carbon dioxide. Heterotrophic bacteria include parasitic types. Typical autotrophic bacteria are phototrophic cyanobacteria, green sulfur-bacteria and some purple bacteria, but also many chemolithotrophic species, such as nitrifying or sulfur-oxidising bacteria. Energy metabolism of bacteria is either based on phototrophy, the use of light through photosynthesis, or on chemotrophy, the use of chemical substances for energy, which are mostly oxidised at the expense of oxygen or alternative electron acceptors (aerobic/anaerobic respiration).

cyanobacteria

Finally, bacteria are further divided into lithotrophs that use inorganic electron donors and organotrophs that use organic compounds as electron donors. Chemotrophic organisms use the respective electron donors for energy conservation (by aerobic/anaerobic respiration or fermentation) and biosynthetic reactions (e.g. carbon dioxide fixation), whereas phototrophic organisms use them only for biosynthetic purposes. Respiratory organisms use chemical compounds as a source of energy by taking electrons from the reduced substrate and transferring them to a terminal electron acceptor in a redox reaction. This reaction releases energy that can be used to synthesise ATP and drive metabolism. In aerobic organisms, oxygen is used as the electron acceptor. In anaerobic organisms other inorganic compounds, such as nitrate, sulfate or carbon dioxide are used as electron acceptors. This leads to the ecologically important processes of denitrification, sulfate reduction and acetogenesis, respectively.

Another way of life of chemotrophs in the absence of possible electron acceptors is fermentation, where the electrons taken from the reduced substrates are transferred to oxidised intermediates to generate reduced fermentation products (e.g. lactate, ethanol, hydrogen, butyric acid). Fermentation is possible, because the energy content of the substrates is higher than that of the products, which allows the organisms to synthesise ATP and drive their metabolism.

These processes are also important in biological responses to pollution; for example, sulfate-reducing bacteria are largely responsible for the production of the highly toxic forms of mercury ( methyl- and dimethylmercury) in the environment. Non-respiratory anaerobes use fermentation to generate energy and reducing power, secreting metabolic by-products (such as ethanol in brewing) as waste. Facultative anaerobes can switch between fermentation and different terminal electron acceptors depending on the environmental conditions in which they find themselves.

Lithotrophic bacteria can use inorganic compounds as a source of energy. Common inorganic electron donors are hydrogen, carbon monoxide, ammonia (leading to nitrification), ferrous iron and other reduced metal ions, and several reduced sulfur compounds. Unusually, the gas methane can be used by methanotrophic bacteria as both a source of electrons and a substrate for carbon anabolism. In both aerobic phototrophy and chemolithotrophy, oxygen is used as a terminal electron acceptor, while under anaerobic conditions inorganic compounds are used instead. Most lithotrophic organisms are autotrophic, whereas organotrophic organisms are heterotrophic.

In addition to fixing carbon dioxide in photosynthesis, some bacteria also fix nitrogen gas (nitrogen fixation) using the enzyme nitrogenase. This environmentally important trait can be found in bacteria of nearly all the metabolic types listed above, but is not universal.

Growth and reproduction


Unlike multicellular organisms, increases in the size of bacteria (cell growth) and their reproduction by cell division are tightly linked in unicellular organisms. Bacteria grow to a fixed size and then reproduce through binary fission, a form of asexual reproduction. In cell division, two identical clone daughter cells are produced. Some bacteria, while still reproducing asexually, form more complex reproductive structures that help disperse the newly formed daughter cells. Examples include fruiting body formation by Myxobacteria and aerial hyphae formation by Streptomyces, or budding. Budding involves a cell forming a protrusion that breaks away and produces a daughter cell.

In the laboratory, bacteria are usually grown using solid or liquid media. Solid growth media such as agar plates are used to isolate pure cultures of a bacterial strain. However, liquid growth media are used when measurement of growth or large volumes of cells are required. Growth in stirred liquid media occurs as an even cell suspension, making the cultures easy to divide and transfer, although isolating single bacteria from liquid media is difficult. The use of selective media (media with specific nutrients added or deficient, or with antibiotics added) can help identify specific organisms.

Most laboratory techniques for growing bacteria use high levels of nutrients to produce large amounts of cells cheaply and quickly. However, in natural environments nutrients are limited, meaning that bacteria cannot continue to reproduce indefinitely. This nutrient limitation has led the evolution of different growth strategies (see r/K selection theory). Some organisms can grow extremely rapidly when nutrients become available, such as the formation of algal (and cyanobacterial) blooms that often occur in lakes during the summer. Other organisms have adaptations to harsh environments, such as the production of multiple antibiotics by Streptomyces that inhibit the growth of competing microorganisms. In nature, many organisms live in communities (e.g. biofilms) which may allow for increased supply of nutrients and protection from environmental stresses. These relationships can be essential for growth of a particular organism or group of organisms (syntrophy).

Bacterial growth follows three phases. When a population of bacteria first enter a high-nutrient environment that allows growth, the cells need to adapt to their new environment. The first phase of growth is the lag phase, a period of slow growth when the cells are adapting to the high-nutrient environment and preparing for fast growth. The lag phase has high biosynthesis rates, as proteins necessary for rapid growth are produced. The second phase of growth is the logarithmic phase (log phase), also known as the exponential phase. The log phase is marked by rapid exponential growth. The rate at which cells grow during this phase is known as the growth rate ( k ), and the time it takes the cells to double is known as the generation time ( g ). During log phase, nutrients are metabolised at maximum speed until one of the nutrients is depleted and starts limiting growth. The final phase of growth is the stationary phase and is caused by depleted nutrients. The cells reduce their metabolic activity and consume non-essential cellular proteins. The stationary phase is a transition from rapid growth to a stress response state and there is increased expression of genes involved in DNA repair, antioxidant metabolism and nutrient transport.

Genetics


Most bacteria have a single circular chromosome that can range in size from only 160,000 base pairs in the endosymbiotic bacteria Candidatus Carsonella ruddii, to 12,200,000 base pairs in the soil-dwelling bacteria Sorangium cellulosum . Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome. The genes in bacterial genomes are usually a single continuous stretch of DNA and although several different types of introns do exist in bacteria, these are much more rare than in eukaryotes.

Bacteria may also contain plasmids, which are small extra-chromosomal DNAs that may contain genes for antibiotic resistance or virulence factors.

Bacteria, as asexual organisms, inherit identical copies of their parent's genes (i.e., they are clonal). However, all bacteria can evolve by selection on changes to their genetic material DNA caused by genetic recombination or mutations. Mutations come from errors made during the replication of DNA or from exposure to mutagens. Mutation rates vary widely among different species of bacteria and even among different clones of a single species of bacteria.

Some bacteria also transfer genetic material between cells. This can occur in three main ways. Firstly, bacteria can take up exogenous DNA from their environment, in a process called transformation. Genes can also be transferred by the process of transduction, when the integration of a bacteriophage introduces foreign DNA into the chromosome. The third method of gene transfer is bacterial conjugation, where DNA is transferred through direct cell contact. This gene acquisition from other bacteria or the environment is called horizontal gene transfer and may be common under natural conditions. Gene transfer is particularly important in antibiotic resistance as it allows the rapid transfer of resistance genes between different pathogens.

Bacteriophages

Bacteriophages are viruses that change the bacterial DNA. Many types of bacteriophage exist, some simply infect and lyse their host bacteria, while others insert into the bacterial chromosome. A bacteriophage can contain genes that contribute to its host's phenotype: for example, in the evolution of Escherichia coli O157:H7 and Clostridium botulinum, the toxin genes in an integrated phage converted a harmless ancestral bacteria into a lethal pathogen. Bacteria resist phage infection through restriction modification systems that degrade foreign DNA, and a system that uses CRISPR sequences to retain fragments of the genomes of phage that the bacteria have come into contact with in the past, which allows them to block virus replication through a form of RNA interference. This CRISPR system provides bacteria with acquired immunity to infection.

Behavior

Secretion

Bacteria frequently secrete chemicals into their environment in order to modify it favorably. The secretions are often proteins and may act as enzymes that digest some form of food in the environment.

Bioluminescence

A few bacteria have chemical systems that generate light. This bioluminescence often occurs in bacteria that live in association with fish, and the light probably serves to attract fish or other large animals.

Multicellularity

( See also: Prokaryote#Sociality)

Bacteria often function as multicellular aggregates known as biofilms, exchanging a variety of molecular signals for inter-cell communication, and engaging in coordinated multicellular behavior.

The communal benefits of multicellular cooperation include a cellular division of labor, accessing resources that cannot effectively be utilized by single cells, collectively defending against antagonists, and optimizing population survival by differentiating into distinct cell types. For example, bacteria in biofilms can have more than 500 times increased resistance to antibacterial agents than individual planktonic bacteria of the same species.

One type of inter-cellular communication by a molecular signal is called quorum sensing, which serves the purpose of determining whether there is a local population density that is sufficiently high that it is productive to invest in processes that are only successful if large numbers of similar organisms behave similarly, as in excreting digestive enzymes or emitting light.

It is thought that bacteria are too small to use pheromones to attract other individuals, as is common among animals.

Movement

Many bacteria can move using a variety of mechanisms: flagella are used for swimming through water; bacterial gliding and twitching motility move bacteria across surfaces; and changes of buoyancy allow vertical motion.

Swimming bacteria frequently move near 10 body lengths per second and a few as fast as 100. This makes them at least as fast as fish, on a relative scale.

In twitching motility, bacterial use their type IV pili as a grappling hook, repeatedly extending it, anchoring it and then retracting it with remarkable force (>80 pN).

Flagella are semi-rigid cylindrical structures that are rotated and function much like the propeller on a ship. Objects as small as bacteria operate a low Reynolds number and cylindrical forms are more efficient that the flat, paddle-like, forms appropriate at human size scale.

Bacterial species differ in the number and arrangement of flagella on their surface; some have a single flagellum (monotrichous), a flagellum at each end (amphitrichous), clusters of flagella at the poles of the cell (lophotrichous), while others have flagella distributed over the entire surface of the cell (peritrichous). The bacterial flagella is the best-understood motility structure in any organism and is made of about 20 proteins, with approximately another 30 proteins required for its regulation and assembly. The flagellum is a rotating structure driven by a reversible motor at the base that uses the electrochemical gradient across the membrane for power. This motor drives the motion of the filament, which acts as a propeller.

Many bacteria (such as E. coli ) have two distinct modes of movement: forward movement (swimming) and tumbling. The tumbling allows them to reorient and makes their movement a three-dimensional random walk. (See external links below for link to videos.) The flagella of a unique group of bacteria, the spirochaetes, are found between two membranes in the periplasmic space. They have a distinctive helical body that twists about as it moves.

Motile bacteria are attracted or repelled by certain stimuli in behaviors called taxes : these include chemotaxis, phototaxis and magnetotaxis. In one peculiar group, the myxobacteria, individual bacteria move together to form waves of cells that then differentiate to form fruiting bodies containing spores. The myxobacteria move only when on solid surfaces, unlike E. coli which is motile in liquid or solid media.

Several Listeria and Shigella species move inside host cells by usurping the cytoskeleton, which is normally used to move organelles inside the cell. By promoting actin polymerization at one pole of their cells, they can form a kind of tail that pushes them through the host cell's cytoplasm.

Classification and identification

Classification seeks to describe the diversity of bacterial species by naming and grouping organisms based on similarities. Bacteria can be classified on the basis of cell structure, cellular metabolism or on differences in cell components such as DNA, fatty acids, pigments, antigens and quinones. While these schemes allowed the identification and classification of bacterial strains, it was unclear whether these differences represented variation between distinct species or between strains of the same species. This uncertainty was due to the lack of distinctive structures in most bacteria, as well as lateral gene transfer between unrelated species. Due to lateral gene transfer, some closely related bacteria can have very different morphologies and metabolisms. To overcome this uncertainty, modern bacterial classification emphasizes molecular systematics, using genetic techniques such as guanine cytosine ratio determination, genome-genome hybridization, as well as sequencing genes that have not undergone extensive lateral gene transfer, such as the rRNA gene. The International Committee on Systematic Bacteriology (ICSB) maintains international rules for the naming of bacteria and taxonomic categories and for the ranking of them in the International Code of Nomenclature of Bacteria.

The term bacteria was traditionally applied to all microscopic, single-celled prokaryotes. However, molecular systematics showed prokaryotic life to consist of two separate domains, originally called Eubacteria and Archaebacteria, but now called Bacteria and Archaea that evolved independently from an ancient common ancestor. The archaea and eukaryotes are more closely related to each other than either is to the bacteria. These two domains, along with Eukarya, are the basis of the three-domain system, which is currently the most widely used classification system in microbiolology.

Identification of bacteria in the laboratory is particularly relevant in medicine, where the correct treatment is determined by the bacterial species causing an infection. Consequently, the need to identify human pathogens was a major impetus for the development of techniques to identify bacteria.
The Gram stain, developed in 1884 by Hans Christian Gram, characterises bacteria based on the structural characteristics of their cell walls. The thick layers of peptidoglycan in the Gram-positive cell wall stain purple, while the thin Gram-negative cell wall appears pink. By combining morphology and Gram-staining, most bacteria can be classified as belonging to one of four groups (Gram-positive cocci, Gram-positive bacilli, Gram-negative cocci and Gram-negative bacilli). Some organisms are best identified by stains other than the Gram stain, particularly mycobacteria or Nocardia, which show acid-fastness on Ziehl-Neelsen or similar stains. Other organisms may need to be identified by their growth in special media, or by other techniques, such as serology.

Culture techniques are designed to promote the growth and identify particular bacteria, while restricting the growth of the other bacteria in the sample. Often these techniques are designed for specific specimens; for example, a sputum sample will be treated to identify organisms that cause pneumonia, while stool specimens are cultured on selective media to identify organisms that cause diarrhoea, while preventing growth of non-pathogenic bacteria. Specimens that are normally sterile, such as blood, urine or spinal fluid, are cultured under conditions designed to grow all possible organisms. Once a pathogenic organism has been isolated, it can be further characterised by its morphology, growth patterns such as ( aerobic or anaerobic growth, patterns of hemolysis) and staining.

As with bacterial classification, identification of bacteria is increasingly using molecular methods. Diagnostics using such DNA-based tools, such as polymerase chain reaction, are increasingly popular due to their specificity and speed, compared to culture-based methods. These methods also allow the detection and identification of viable but nonculturable cells that are metabolically active but non-dividing.

Interactions with other organisms

Despite their apparent simplicity, bacteria can form complex associations with other organisms. These symbiotic associations can be divided into parasitism, mutualism and commensalism. Due to their small size, commensal bacteria are ubiquitous and grow on animals and plants exactly as they will grow on any other surface. However, their growth can be increased by warmth and sweat, and large populations of these organisms in humans are the cause of body odor.

Predators

Some species of bacteria kill and then consume other microorganisms, these species called predatory bacteria . These include organisms such as Myxococcus xanthus, which forms swarms of cells that kill and digest any bacteria they encounter. Other bacterial predators either attach to their prey in order to digest them and absorb nutrients, such as Vampirococcus, or invade another cell and multiply inside the cytosol, such as Daptobacter . These predatory bacteria are thought to have evolved from saprophages that consumed dead microorganisms, through adaptations that allowed them to entrap and kill other organisms.

Mutualists

Certain bacteria form close spatial associations that are essential for their survival. One such mutualistic association, called interspecies hydrogen transfer, occurs between clusters of anaerobic bacteria that consume organic acids such as butyric acid or propionic acid and produce hydrogen, and methanogenic Archaea that consume hydrogen. The bacteria in this association are unable to consume the organic acids as this reaction produces hydrogen that accumulates in their surroundings. Only the intimate association with the hydrogen-consuming Archaea keeps the hydrogen concentration low enough to allow the bacteria to grow.

In soil, microorganisms which reside in the rhizosphere (a zone that includes the root surface and the soil that adheres to the root after gentle shaking) carry out nitrogen fixation, converting nitrogen gas to nitrogenous compounds. This serves to provide an easily absorbable form of nitrogen for many plants, which cannot fix nitrogen themselves. Many other bacteria are found as symbionts in humans and other organisms. For example, the presence of over 1,000 bacterial species in the normal human gut flora of the intestines can contribute to gut immunity, synthesise vitamins such as folic acid, vitamin K and biotin, convert milk protein to lactic acid (see Lactobacillus ), as well as fermenting complex undigestible carbohydrates. The presence of this gut flora also inhibits the growth of potentially pathogenic bacteria (usually through competitive exclusion) and these beneficial bacteria are consequently sold as probiotic dietary supplements.

Pathogens

If bacteria form a parasitic association with other organisms, they are classed as pathogens. Pathogenic bacteria are a major cause of human death and disease and cause infections such as tetanus, typhoid fever, diphtheria, syphilis, cholera, foodborne illness, leprosy and tuberculosis. A pathogenic cause for a known medical disease may only be discovered many years after, as was the case with Helicobacter pylori and peptic ulcer disease. Bacterial diseases are also important in agriculture, with bacteria causing leaf spot, fire blight and wilts in plants, as well as Johne's disease, mastitis, salmonella and anthrax in farm animals.

Each species of pathogen has a characteristic spectrum of interactions with its human hosts. Some organisms, such as Staphylococcus or Streptococcus, can cause skin infections, pneumonia, meningitis and even overwhelming sepsis, a systemic inflammatory response producing shock, massive vasodilation and death. Yet these organisms are also part of the normal human flora and usually exist on the skin or in the nose without causing any disease at all. Other organisms invariably cause disease in humans, such as the Rickettsia, which are obligate intracellular parasites able to grow and reproduce only within the cells of other organisms. One species of Rickettsia causes typhus, while another causes Rocky Mountain spotted fever. Chlamydia, another phylum of obligate intracellular parasites, contains species that can cause pneumonia, or urinary tract infection and may be involved in coronary heart disease. Finally, some species such as Pseudomonas aeruginosa, Burkholderia cenocepacia, and Mycobacterium avium are opportunistic pathogens and cause disease mainly in people suffering from immunosuppression or cystic fibrosis.

Overview of bacterial infections and main species involved.

Bacterial infections may be treated with antibiotics, which are classified as bacteriocidal if they kill bacteria, or bacteriostatic if they just prevent bacterial growth. There are many types of antibiotics and each class inhibits a process that is different in the pathogen from that found in the host. An example of how antibiotics produce selective toxicity are chloramphenicol and puromycin, which inhibit the bacterial ribosome, but not the structurally different eukaryotic ribosome. Antibiotics are used both in treating human disease and in intensive farming to promote animal growth, where they may be contributing to the rapid development of antibiotic resistance in bacterial populations. Infections can be prevented by antiseptic measures such as sterilizating the skin prior to piercing it with the needle of a syringe, and by proper care of indwelling catheters. Surgical and dental instruments are also sterilized to prevent contamination by bacteria. Disinfectants such as bleach are used to kill bacteria or other pathogens on surfaces to prevent contamination and further reduce the risk of infection.

Significance in technology and industry


Bacteria, often lactic acid bacteria such as Lactobacillus and Lactococcus, in combination with yeasts and molds, have been used for thousands of years in the preparation of fermented foods such as cheese, pickles, soy sauce, sauerkraut, vinegar, wine and yoghurt.

The ability of bacteria to degrade a variety of organic compounds is remarkable and has been used in waste processing and bioremediation. Bacteria capable of digesting the hydrocarbons in petroleum are often used to clean up oil spills. Fertilizer was added to some of the beaches in Prince William Sound in an attempt to promote the growth of these naturally occurring bacteria after the infamous 1989 Exxon Valdez oil spill. These efforts were effective on beaches that were not too thickly covered in oil. Bacteria are also used for the bioremediation of industrial toxic wastes. In the chemical industry, bacteria are most important in the production of enantiomerically pure chemicals for use as pharmaceuticals or agrichemicals.

Bacteria can also be used in the place of pesticides in the biological pest control. This commonly involves Bacillus thuringiensis (also called BT), a Gram-positive, soil dwelling bacterium. Subspecies of this bacteria are used as a Lepidopteran-specific insecticides under trade names such as Dipel and Thuricide. Because of their specificity, these pesticides are regarded as environmentally friendly, with little or no effect on humans, wildlife, pollinators and most other beneficial insects.

Because of their ability to quickly grow and the relative ease with which they can be manipulated, bacteria are the workhorses for the fields of molecular biology, genetics and biochemistry. By making mutations in bacterial DNA and examining the resulting phenotypes, scientists can determine the function of genes, enzymes and metabolic pathways in bacteria, then apply this knowledge to more complex organisms. This aim of understanding the biochemistry of a cell reaches its most complex expression in the synthesis of huge amounts of enzyme kinetic and gene expression data into mathematical models of entire organisms. This is achievable in some well-studied bacteria, with models of Escherichia coli metabolism now being produced and tested. This understanding of bacterial metabolism and genetics allows the use of biotechnology to bioengineer bacteria for the production of therapeutic proteins, such as insulin, growth factors, or antibodies.

See also

Biotechnology
Extremophiles
List of bacterial orders
Transgenic bacteria
Psychrotrophic bacteria
Microorganism
International Code of Nomenclature of Bacteria

Notes

α. The word bacteria derives from the Greek βακτήριον, baktērion, meaning small staff .

References

Further reading

External links


MicrobeWiki, an extensive wiki about bacteria and viruses
Bacteria which affect crops and other plants
Bacterial Nomenclature Up-To-Date from DSMZ
Genera of the domain Bacteria - list of Prokaryotic names with Standing in Nomenclature
The largest bacteria
Tree of Life: Eubacteria
Videos of bacteria swimming and tumbling, use of optical tweezers and other videos.
Planet of the Bacteria by Stephen Jay Gould
On-line text book on bacteriology
Animated guide to bacterial cell structure.
Bacteria Make Major Evolutionary Shift in the Lab
Cell-Cell Communication in Bacteria on-line lecture by Bonnie Bassler, and TED: Discovering bacteria's amazing communication system
Online collaboration for bacterial taxonomy.
Parts of a bacterial cell
Bacterial Chemotaxis Interactive Simulator - A web-app that uses several simple algorithms to simulate bacterial chemotaxis.



TUBERCULOSIS CUTIS ORIFICIALIS

Tuberculosis cutis orificialis (also known as Acute tuberculous ulcer,

See also

Scrofuloderma
Skin lesion
List of cutaneous conditions

References




 
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