Mycobacterium tuberculosis | |
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M. tuberculosis bacterial colonies | |
Scientific classification | |
Kingdom: | Bacteria |
Phylum: | Actinobacteria |
Class: | Actinobacteria |
Order: | Actinomycetales |
Suborder: | Corynebacterineae |
Family: | Mycobacteriaceae |
Genus: | Mycobacterium |
Species: | M. tuberculosis |
Binomial name | |
Mycobacterium tuberculosis Zopf 1883 |
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Synonyms | |
Tubercle bacillus Koch 1882 |
Mycobacterium tuberculosis (MTB) is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis (TB).[1] First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface (primarily mycolic acid), which makes the cells impervious to Gram staining, so acid-fast detection techniques are used, instead. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, MTB infects the lungs. The most frequently used diagnostic methods for TB are the tuberculin skin test, acid-fast stain, and chest radiographs.[1]
The M. tuberculosis genome was sequenced in 1998.[2][3]
Contents |
Pathophysiology
M. tuberculosis requires oxygen to grow. It does not retain any bacteriological stain due to high lipid content in its wall, and thus is neither Gram-positive nor Gram-negative; hence Ziehl-Neelsen staining, or acid-fast staining, is used. While mycobacteria do not seem to fit the Gram-positive category from an empirical standpoint (i.e., they do not retain the crystal violet stain), they are classified as acid-fast Gram-positive bacteria due to their lack of an outer cell membrane.[1]
M. tuberculosis divides every 15–20 hours, which is extremely slow compared to other bacteria, which tend to have division times measured in minutes (Escherichia coli can divide roughly every 20 minutes). It is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall, rich in lipids (e.g., mycolic acid), is likely responsible for this resistance and is a key virulence factor.[4]
When in the lungs, M. tuberculosis is taken up by alveolar macrophages, but they are unable to digest the bacterium. Its cell wall prevents the fusion of the phagosome with a lysosome. Specifically, M. tuberculosis blocks the bridging molecule, early endosomal autoantigen 1 (EEA1); however, this blockade does not prevent fusion of vesicles filled with nutrients. Consequently, the bacteria multiply unchecked within the macrophage. The bacteria also carried the UreC gene, which prevents acidification of the phagosome.[5] The bacteria also evade macrophage-killing by neutralizing reactive nitrogen intermediates.[citation needed]
The ability to construct M. tuberculosis mutants and test individual gene products for specific functions has significantly advanced our understanding of the pathogenesis and virulence factors of M. tuberculosis. Many secreted and exported proteins are known to be important in pathogenesis.[6]
Strain variation
M. tuberculosis comes from the genus Mycobacterium, which is composed of approximately 100 recognized and proposed species. The most familiar of the species are M. tuberculosis and M. leprae (leprosy).[7] M. tuberculosis appears to be genetically diverse, which results in significant phenotypic differences between clinical isolates. M. tuberculosis exhibits a biogeographic population structure, and different strain lineages are associated with different geographic regions. Phenotypic studies suggest this strain variation never has implications for the development of new diagnostics and vaccines. Microevolutionary variation affects the relative fitness and transmission dynamics of antibiotic-resistant strains.[8]
Hypervirulent strains
Mycobacterium outbreaks are often caused by hypervirulent strains of M. tuberculosis. In laboratory experiments, these clinical isolates elicit unusual immunopathology, and may be either hyperinflammatory or hypoinflammatory. Studies have shown the majority of hypervirulent mutants have deletions in their cell wall-modifying enzymes or regulators that respond to environmental stimuli. Studies of these mutants have indicated the mechanisms that enable M. tuberculosis to mask its full pathogenic potential, inducing a granuloma that provides a protective niche, and enable the bacilli to sustain a long-term, persistent infection.[9]
Microscopy
M. tuberculosis is characterized by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei. Organisms are identified by their red color on acid-fast staining.
Genome
The genome of the H37Rv strain was published in 1998.[10] Its size is 4 million base pairs, with 3959 genes; 40% of these genes have had their function characterised, with possible function postulated for another 44%. Within the genome are also six pseudogenes.
The genome contains 250 genes involved in fatty acid metabolism, with 39 of these involved in the polyketide metabolism generating the waxy coat. Such large numbers of conserved genes show the evolutionary importance of the waxy coat to pathogen survival.
About 10% of the coding capacity is taken up by two clustered gene families that encode acidic, glycine-rich proteins. These proteins have a conserved N-terminal motif, deletion of which impairs growth in macrophages and granulomas.[11]
Nine noncoding sRNAs have been characterised in M. tuberculosis,[12] with a further 56 predicted in a bioinformatics screen.[13]
History
M. tuberculosis, then known as the "tubercle bacillus", was first described on 24 March 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905; the bacterium is also known as "Koch's bacillus".[14]
Tuberculosis has existed throughout history, but the name has changed frequently over time. In 1720, though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his A Theory of Consumption, tuberculosis may be caused by small living creatures that are transmitted through the air to other patients.[15]
See also
References
- ^ a b c Ismael Kassim, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
- ^ Cole ST, Brosch R, Parkhill J, et al. (June 1998). "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence". Nature 393 (6685): 537–44. doi:10.1038/31159. PMID 9634230.
- ^ Camus JC, Pryor MJ, Médigue C, Cole ST (October 2002). "Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv". Microbiology (Reading, Engl.) 148 (Pt 10): 2967–73. PMID 12368430. http://mic.sgmjournals.org/cgi/pmidlookup?view=long&pmid=12368430.
- ^ Murray PR, Rosenthal KS, Pfaller MA (2005). Medical Microbiology. Elsevier Mosby.
- ^ Bell E (October 2005). "Vaccines: A souped-up version of BCG". Nature Reviews Immunology 5 (10): 746. doi:10.1038/nri1720.
- ^ Wooldridge K (editor) (2009). Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis. Caister Academic Press. ISBN 978-1-904455-42-4.
- ^ (Page 576;Textbook of Diagnostic Microbiology, Mahon, Lehman, Manuselis)
- ^ Gagneux S (2009). "Strain Variation and Evolution". Mycobacterium: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-40-0.
- ^ Casali N (2009). "Hypervirulent Mycobacterium tuberculosis". Mycobacterium: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-40-0.
- ^ "Mycobacterium tuberculosis". Sanger Institute. 2007-03-29. http://www.sanger.ac.uk/Projects/M_tuberculosis/. Retrieved 2008-11-16.
- ^ Glickman MS, Jacobs WR (February 2001). "Microbial pathogenesis of Mycobacterium tuberculosis: dawn of a discipline". Cell 104 (4): 477–85. doi:10.1016/S0092-8674(01)00236-7. PMID 11239406. http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(01)00236-7.
- ^ Arnvig KB, Young DB (August 2009). "Identification of small RNAs in Mycobacterium tuberculosis". Mol. Microbiol. 73 (3): 397–408. doi:10.1111/j.1365-2958.2009.06777.x. PMC 2764107. PMID 19555452. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0950-382X&date=2009&volume=73&issue=3&spage=397. Retrieved 2010-08-31.
- ^ Livny J, Brencic A, Lory S, Waldor MK (2006). "Identification of 17 Pseudomonas aeruginosa sRNAs and prediction of sRNA-encoding genes in 10 diverse pathogens using the bioinformatic tool sRNAPredict2". Nucleic Acids Res. 34 (12): 3484–93. doi:10.1093/nar/gkl453. PMC 1524904. PMID 16870723. http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16870723. Retrieved 2010-08-31.[dead link]
- ^ "Robert Koch and Tuberculosis: Koch's Famous Lecture". Nobel Foundation. 2008. http://nobelprize.org/educational_games/medicine/tuberculosis/readmore.html. Retrieved 2008-11-18.
- ^ "Tuberculosis History Timeline". http://www.mycobacteriumtuberculosis.net/history.html. Retrieved 2010-06-18.