Mycobacterium avium subspecies paratuberculosis

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Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate pathogenic bacterium in the genus Mycobacterium.[1] It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps the human disease Crohn's disease. The type strain is ATCC 19698 (equivalent to CIP 103963 or DSM 44133).[2]

Pathophysiology[edit]

MAP causes Johne's disease in cattle and other ruminants, and it has long been suspected as a causative agent in Crohn's disease in humans;[3] this connection is controversial.[4]

Recent studies have shown that MAP present in milk can survive pasteurization, which has raised human health concerns due to the widespread nature of MAP in modern dairy herds. MAP survival during pasteurization is dependent on the D72C-value of the strains present and their concentration in milk. It is heat resistant and is capable of sequestering itself inside white blood cells, which may contribute to its persistence in milk. It has also been reported to survive chlorination in municipal water supplies.

MAP is a slow growing organism and is difficult to culture. Bacterial cultures were regarded as Gold standards for detection of MAP. Detection is very limited in fresh tissues, food, and water.

It is not susceptible to antituberculosis drugs (which can generally kill Mycobacterium tuberculosis). MAP is susceptible to antibiotics used to treat Mycobacterium avium disease, such as rifabutin and clarithromycin, however the capacity of these antibiotics to eradicate MAP infection in vivo has not been established.

Crohn's disease[edit]

MAP is recognized as a multi-host mycobacterial pathogen with a proven specific ability to initiate and maintain systemic infection and chronic inflammation of the intestine of a range of histopathological types in many animal species, including primates.[5]

On the assumption that MAP is a causative agent in Crohn's disease, the Australian biotechnology company Giaconda is seeking to commercialize a combination of rifabutin, clarithromycin, and clofazimine as a potential drug therapy, called Myoconda, for Crohn's. As of April 2007, Giaconda received United States FDA IND approval for a new Phase 2/3 trial.[6]

MAP has been found in larger numbers within the intestines of Crohn's disease patients[7] than those with ulcerative colitis and healthy controls.

Genome[edit]

The genome of MAP strain K-10 was sequenced in 2005 and found to consist of a single circular chromosome of 4,829,781 base pairs, and to encode 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon.[8]

See also[edit]

References[edit]

  1. ^ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9. 
  2. ^ Thorel M, Krichevsky M, Lévy-Frébault V (1990). "Numerical taxonomy of mycobactin-dependent mycobacteria, amended description of Mycobacterium avium, and description of Mycobacterium avium subsp. avium subsp. nov., Mycobacterium avium subsp. paratuberculosis subsp. nov., and Mycobacterium avium subsp. silvaticum subsp. nov". Int J Syst Bacteriol 40 (3): 254–60. doi:10.1099/00207713-40-3-254. PMID 2397193. 
  3. ^ Hermon-Taylor, J (2009). "Mycobacterium avium subspecies paratuberculosis, Crohn's disease and the Doomsday scenario". Gut Pathogens 1 (15): 15. doi:10.1186/1757-4749-1-15. PMC 2718892. PMID 19602288. 
  4. ^ Freeman H, Noble M (2005). "Lack of evidence for Mycobacterium avium subspecies paratuberculosis in Crohn's disease regulation of immunity". Inflammatory Bowel Diseases 11 (8): 782–3. doi:10.1097/01.MIB.0000179317.27132.24. PMID 16043998. 
  5. ^ "Johne's Information Center". Retrieved 2008-06-13. 
  6. ^ http://www.biotechnologynews.net/storyview.asp?storyid=97714&sectionsource=s0
  7. ^ Sanderson JD, Moss MT, Tizard ML, Hermon-Taylor J (1992). "Mycobacterium paratuberculosis DNA in Crohn's disease tissue". Gut 33 (7): 890–6. doi:10.1136/gut.33.7.890. PMC 1379400. PMID 1644328. 
  8. ^ Li L, Bannantine J, Zhang Q, Amonsin A, May B, Alt D, Banerji N, Kanjilal S, Kapur V (2005). "The complete genome sequence of Mycobacterium avium subspecies paratuberculosis". Proc Natl Acad Sci USA 102 (35): 12344–9. doi:10.1073/pnas.0505662102. PMC 1194940. PMID 16116077.