A Deletion Defining A Common Asian Lineage Of Mycobacterium Tuberculosis Associates With Immune Subversion.
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Date
2006-10Author
Newton, SM
Smith, RJ
Wilkinson, KA
Nicol, MP
Garton, NJ
Staples, KJ
Stewart, GR
Wain, JR
Martineau, AR
Fandrich, S
Smallie, T
Foxwell, B
Al-Obaidi, A
Shafi, J
Rajakumar, K
Kampmann, B
Andrew, P W
Ziegler-Heitbrock, L
Barer, MR
Wilkinson., RJ
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.
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http://hinari-gw.who.int/whalecomwww.ncbi.nlm.nih.gov/whalecom0/pubmed/17028173http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/44447
Citation
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15594-8. Epub 2006 Oct 6.Publisher
University of Nairobi Institute of Tropica and Infectious Diseases(UNITID)
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- Faculty of Health Sciences (FHS) [10377]