Mycobacterium tuberculosis

Mycobacterium tuberculosis, the bacteria that cause tuberculosis. Source: CDC.

Mycobacterium tuberculosis is a member of the Mycobacterium tuberculosis complex (MTBC) of bacteria that cause human and animal tuberculosis.The bacteria usually attack the lungs, but they can also damage other parts of the body. The organism spreads through the air when a person with tuberculosis TB of the lungs or throat coughs, sneezes or talks.

Effect on Humans

As the most common causative agent of tuberculosis and extrapulmonary tuberculosis, M. tuberculosis is responsible for an enormous burden of disability and death throughout the world.

Microbiology

M. tuberculosis as pink rods containing the Ziehl-Neelsen stain. Source: CDC.

The bacterium is a member of the mycobacteria family and is unusual in several respects. It grows slowly, and has an unusually high content of lipids in its cell wall. As such, it is resistant to many antibiotics (like penicillins), and also that it can more easily become resistant to antibiotics. It is an obligate aerobe (meaning it needs high concentrations of oxygen to multiply); that is why its predilection for highly oxygenated organs such as the upper lobes of the lungs and the kidney.

Diagnosis

M. tuberculosis in a sputum smear is stained using fluorescent auramine with acridine orange counterstain. Source: CDC.

Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. Immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI).^[1]

A common test used to check whether or not a person has been exposed to TB is called the purified protein derivative, or PPD. It consists of a small portion of the bacteria (that no longer causes disease), and is injected just under the skin. In 48 to 72 hours, the injection site is examined for evidence of an immune response.^[2] A positive test (an area of redness and hardness larger 10 mm in size) indicates that a person has sensitized white blood that are reacting with antigens from TB organisms. This indicates that the person has been exposed to TB in the past, but does not mean that the person has active disease or is shedding enough organisms to infect other people.

Treatment

Multidrug therapy is used to prevent emergence of drug-resistance during the treatment period. So, if the bacteria become resistant to one of the drugs it is still covered by the others. Although patient's sputum becomes noninfectious within 2-3 of treatment, the need for a longer therapy time is attributed to:

1. Intracellular location of the organism.
2. Caseous (like cheese) material, which blocks penetration by the drug.
3. Slow growth of the bacteria.
4. Metabolically active "persisters" within the affected region.

See Tuberculosis for more information.

Antimicrobial resistance

Drug susceptibility test on Mycobacterium tuberculosis bacteria. Source: CDC

Resistance to INH (Isoniazid) and other drugs used for tuberculosis treatment are seen with increased frequency in the United States, some European countries, Southeast Asia and Latin America.^[3] Mutidrug resistance is seen more commonly in AIDS, usually to both INH and Rifampin.

History

Mycobacterial disease was probably present in cattle long before humans, and may have been transferred to humans when cattle became domesticated between 8000-4000 BC.^[4] There is evidence of human infection by M. bovis, leading to the hypothesis that M. tuberculosis is a human-specialized form of M. bovis that developed among cattle-using Indo-Europeans. These people then spread the disease during their migration into western Europe from Eurasia. By 1000 BC, M. tuberculosis and pulmonary TB had spread throughout the known world.

The organism was first seen by Robert Koch in 1882, at a time when TB was causing more than 10% of all deaths in Europe. Koch was awarded the Nobel Prize in 1905 for his work.^[5]

The complete sequence of the organism's genome was determined and published in 1998.^[6]

Habitat

Humans are the natural reservoir (source) of M. tuberculosis; there is no animal reservoir.

References

1. ↑ Cho SN. Current issues on molecular and immunological diagnosis of tuberculosis. Yonsei Med J. 2007 Jun 30;48(3):347-59. Abstract PDF
2. ↑ Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis. 1993 Dec;17(6):968-75. Abstract
3. ↑ Kruijshaar ME, Watson JM, Drobniewski F, et. al, Increasing antituberculosis drug resistance in the United Kingdom: analysis of National Surveillance Data. BMJ. 2008 May 31;336(7655):1231-4 Abstract Full Text PDF
4. ↑ Sola C, Filliol I, Legrand E, Mokrousov I, Rastogi N. Mycobacterium tuberculosis phylogeny reconstruction based on combined numerical analysis with IS1081, IS6110, VNTR, and DR-based spoligotyping suggests the existence of two new phylogeographical clades. J Mol Evol. 2001 Dec;53(6):680-9. Abstract
5. ↑ The Nobel Prize in Physiology or Medicine 1905. "For his investigations and discoveries in relation to tuberculosis:" Robert Koch
6. ↑ Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. Abstract Full Text PDF