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 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. Professor John Hermon-Taylor of Kings College London is developing a new vector type anti MAP vaccine which is both curative and preventative. He is also developing a companion MAP blood test.

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

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 was seeking to develop a combination of rifabutin, clarithromycin, and clofazimine as a potential drug therapy, called Myoconda, for Crohn's. In August 2010 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) acquired the rights to Myoconda from Giaconda to further develop and commercialize. RedHill’s new formulation of Myoconda combination therapy is called RHB-104. RedHill’s RHB-104 is currently in a first Phase III study for the treatment of Crohn’s disease (the MAP US study). RHB-104 is a proprietary and potentially groundbreaking oral antibiotic combination therapy, with potent intracellular, anti-mycobacterial and anti-inflammatory properties. RHB-104 is based on increasing evidence supporting the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients. RedHill is also conducting a Phase IIa, proof-of-concept clinical study, evaluating RHB-104 as an add-on therapy to interferon beta-1a in patients treated for relapsing-remitting multiple sclerosis (the CEASE MS study).


MAP has been found in larger numbers within the intestines of Crohn's disease patients[6] 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.[7]

See also

References

  1. ↑ Ryan KJ; Ray CG, eds. (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 2718892Freely accessible. 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. ↑ 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 1379400Freely accessible. PMID 1644328.
  7. ↑ 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 1194940Freely accessible. PMID 16116077.
This article is issued from Wikipedia - version of the 12/2/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.