Mycobacterium tuberculosis 392019 223156945 2008-07-02T20:34:21Z 129.112.109.252 {{Taxobox | color = lightgrey | name = ''Mycobacterium tuberculosis'' | image = TB_Culture.jpg | image_width = 270px | image_caption = ''M. tuberculosis'' bacterial colonies | regnum = [[Bacterium|Bacteria]] | phylum = [[Actinobacteria]] | class = [[Actinobacteria]] | subclass = [[Actinobacteridae]] | ordo = [[Actinomycetales]] | subordo = [[Corynebacterineae]] | familia = [[Mycobacterium|Mycobacteriaceae]] | genus = ''[[Mycobacterium]]'' | species = '''''M. tuberculosis''''' | binomial = ''Mycobacterium tuberculosis'' | binomial_authority = Zopf 1883 }} '''''Mycobacterium tuberculosis''''' is the [[bacterium]] that causes most cases of [[tuberculosis]].<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 }}</ref> ==History== ''M. tuberculosis'', then known as the "[[Tubercle (anatomy)|tubercle]] bacillus," was first described on [[March 24]], [[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 ''[[Robert Koch|Koch's]] bacillus''. The ''M. tuberculosis'' [[genome]] was [[sequenced]] in [[1998]]<ref>{{cite journal | author = Cole ST; Brosch R; Parkhill J; ''et al''. | title = Deciphering the biology of ''Mycobacterium tuberculosis'' from the complete genome sequence | journal = Nature | year = 1998 | volume = 393 | pages = 537&ndash;544 | doi=10.1038/31159 }}</ref><ref>{{cite journal | author = Camus JC; Pryor MJ; Medigue C; Cole ST. | title = Re-annotation of the genome sequence of ''Mycobacterium tuberculosis'' H37Rv | journal = Microbiology | year = 148 | volume = 2002 | pages = 2967&ndash;2973 | url= http://mic.sgmjournals.org/cgi/content/full/148/10/2967?view=full&pmid=12368430 | pmid = 12368430}}</ref> ==Physiology== ''M. tuberculosis'' is an [[obligate aerobe]] (weakly [[Gram-positive]] [[mycobacterium]], hence [[Ziehl-Neelsen staining]] (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 membrane|outer cell membrane]].<ref name=Sherris /> ''M. tuberculosis'' divides every 15 to 20 hours, which is extremely slow compared to other bacteria, which tend to have division times measured in minutes (for example, ''E. coli'' can divide roughly every 20 minutes). It is a small [[bacillus]] that can withstand weak [[disinfectant]]s 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.<ref>Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2005). ''Medical Microbiology'', Elsevier Mosby.</ref> 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<ref>Vaccines: A souped-up version of BCG, Bell, Nature Reviews Immunology 5, 746, (October 2005)</ref>. The bacteria also evade macrophage killing by neutralizing reactive nitrogen intermediates. ==Genome== The genome of the H37Rv strain was published in 1998.<Ref>http://www.sanger.ac.uk/Projects/M_tuberculosis/</ref> It's 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 6 pseudogenes. The geneome 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 shows the evolutionary importance of the waxy coat to pathogen survival. 10% of the coding capacity is taken up by 2 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.<ref>Microbial Pathogenesis of Mycobacterium tuberculosis: Dawn of a Discipline, Glickman; Jacobs, ''Cell'', Vol 104 Is 4, pg477 - 485</ref> ==Diagnosis== [[Sputum]] is taken in 3 successive mornings as the number of organisms could be low, and the specimen is treated with 3% [[Potassium hydroxide|KOH]] or [[Sodium hydroxide|NaOH]] for [[liquefaction]] and [[decontamination]]. [[Gram stain]] should never be performed, as the organism is an "[[acid-fast]] bacillus" (AFB), meaning that it retains certain stains after being treated with acidic solution. In the most common staining technique, the [[Ziehl-Neelsen stain]], AFB are stained a bright red, which stands out clearly against a blue background; therefore, the bacteria are sometimes called ''red snappers''.<ref>{{cite journal |author=Flowers T |title=Quarantining the noncompliant TB patient: catching the "Red Snapper" |journal=Journal of health and hospital law : a publication of the American Academy of Hospital Attorneys of the American Hospital Association |volume=28 |issue=2 |pages=== h == 95–105 |year=1995 |pmid=10141473 |doi=}}</ref> The reason for the acid-fast staining is because of its thick waxy cell wall.<ref name=Brock>{{cite book | author = Madigan, Michael; Martinko, John (editors) | title = Brock Biology of Microorganisms | edition = 11th ed. | publisher = Prentice Hall | year = 2005 | id = ISBN 0-13-144329-1 }}</ref> The waxy quality of the [[cell wall]] is mainly due to the presence of [[mycolic acid]]s. This waxy cell wall also is responsible for the typical [[Caseous necrosis|caseous]] [[granuloma]] formation in tuberculosis. The component responsible, [[trehalose dimycolate]], is called the cord factor. A grading system exists for interpretation of the microscopic findings based on the number of organisms observed in each field. It should be noted that the Ziehl- Neelsen stain is positive in only 50% of cases, which means that, even if no organisms are observed, further investigation is still required. Acid-fast bacilli can also be visualized by [[fluorescent microscopy]] using [[auramine-rhodamine stain]] for screening, which makes them appear somewhat golden in color. Also, ''M. tuberculosis'' is grown on a selective medium known as [[Lowenstein-Jensen medium]], which has traditionally been used for this purpose. However, this method is quite slow, as this organism requires 6-8 weeks to grow, which delays reporting of results. A faster results can now be obtained using Middlebrook medium. It should be taken into consideration that during an advanced stage of tuberculosis, the organism may infect almost any part of the body, which means that a specimen should appropriately be chosen (e.g. intestinal tuberculosis-[[human feces|stool]]). ==See also== *[[Philip D'Arcy Hart]] *[[Tuberculosis]] ==References== {{reflist}} ==External links== *[http://www.biohealthbase.org/GSearch/statsAutomation.do?decorator=Mycobacterium Database of ''Mycobacterium tuberculosis'' genome sequences and related information.] [[Category:Acid fast bacilli]] [[Category:Corynebacterineae]] [[ca:Mycobacterium tuberculosis]] [[de:Mycobacterium tuberculosis]] [[es:Mycobacterium tuberculosis]] [[fa:میکوباکتریوم توبرکلوزیس]] [[fr:Mycobacterium tuberculosis]] [[ko:결핵균]] [[id:Mycobacterium tuberculosis]] [[it:Mycobacterium tuberculosis]] [[he:Mycobacterium tuberculosis]] [[la:Mycobacterium tuberculosis]] [[hu:Mycobacterium tuberculosis]] [[nl:Mycobacterium tuberculosis]] [[ja:結核菌]] [[no:Mycobacterium tuberculosis]] [[pl:Prątek gruźlicy]] [[pt:Mycobacterium tuberculosis]] [[ro:Mycobacterium tuberculosis]] [[ru:Mycobacterium tuberculosis]] [[sl:Mycobacterium tuberculosis]] [[fi:Mycobacterium tuberculosis]] [[tr:Mycobacterium tuberculosis]] [[uk:Mycobacterium tuberculosis]] [[zh:結核桿菌]]