Mycobacterium avium subspecies paratuberculosis

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

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 D_72C-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.

Even though MAP is hardy, it is slow growing and fastidious, which means it is difficult to culture. Many negative studies for MAP presence in living tissue, food, and water have used culture methods to determine whether the bacteria are present. Due to recent advances in our knowledge of the bacterium, some or all of these studies may need to be re-evaluated on the basis of culture methodology.

MAP infections, like with most mycobacteria, are difficult to treat. It is not susceptible to antituberculosis drugs (which can generally kill Mycobacterium tuberculosis), but can only be treated with a combination of antibiotics such as rifabutin and a macrolide such as clarithromycin. Treatment regimens can last years.^[5][6]

Crohn's disease

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.^[7]

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.^[8]

MAP has been found in larger numbers within the intestines of Crohn's disease patients^[9] than those with ulcerative colitis and healthy controls.

Genome

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.^[10]

See also

• zoonose
• Crohn's disease
• Johne's disease

References

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2718892. 
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. doi:10.1097/01.MIB.0000179317.27132.24. PMID 16043998. http://www3.interscience.wiley.com/cgi-bin/fulltext/113522086/HTMLSTART. 
5. ^ BIOLOGY RESISTANCE - JOHNE'S INFORMATION CENTER
6. ^ Two-year outcomes analysis of Crohn's Disease treated with rifabutin and macrolide antibiotics.-(G.P.H. Gui, P.R.S.Thomas, M.L.V.Tizard, J.Lake, J.D.Sanderson and J.Hermon-Taylor.) University Department of Surgery, St Georges Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.
7. ^ "Johne's Information Center". http://www.johnes.org/. Retrieved 2008-06-13. 
8. ^ http://www.biotechnologynews.net/storyview.asp?storyid=97714&sectionsource=s0
9. ^ Mycobacterium paratuberculosis DNA in Crohn's disease tissue. - J D Sanderson, M T Moss, M L Tizard, J Hermon-Taylor (Gut 1992;33:890-896; doi:10.1136/gut.33.7.890)
10. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1194940.