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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion
Proceedings of the National Academy of Sciences of the United States of America, Volume 103, No. 42, Year 2006
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Description
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. © 2006 by The National Academy of Sciences of the USA.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1622867/bin/pnas_0604283103_index.html
Authors & Co-Authors
Newton, Sandra M.
United Kingdom, London
Wellcome Trust
Smith, Rebecca J.
United Kingdom, Leicester
Leicester Medical School
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
Wellcome Trust
South Africa, Cape Town
Faculty of Health Sciences
Nicol, Mark P.
South Africa, Cape Town
Faculty of Health Sciences
Garton, Natalie J.
United Kingdom, Leicester
Leicester Medical School
Staples, Karl J.
United Kingdom, Leicester
Leicester Medical School
Stewart, Graham R.
United Kingdom, London
Wellcome Trust
Wain, John R.
United Kingdom, London
Wellcome Trust
Martineau, Adrian R.
United Kingdom, London
Wellcome Trust
South Africa, Cape Town
Faculty of Health Sciences
Fandrich, Sarah
United Kingdom, Leicester
Leicester Medical School
Smallie, Tim
United Kingdom, London
Wellcome Trust
Foxwell, Brian M.
United Kingdom, London
Wellcome Trust
Al-Obaidi, Ahmed
United Kingdom, Leicester
Leicester Medical School
Shafi, Jamila
United Kingdom, Leicester
Leicester Medical School
Rajakumar, Kumar
United Kingdom, Leicester
Leicester Medical School
Kampmann, Beate B.
United Kingdom, London
Wellcome Trust
South Africa, Cape Town
Faculty of Health Sciences
Andrew, Peter W.
United Kingdom, Leicester
Leicester Medical School
Ziegler-Heitbrock, Loems
United Kingdom, Leicester
Leicester Medical School
Barer, Michael R.
United Kingdom, Leicester
Leicester Medical School
Wilkinson, Robert J.
United Kingdom, London
Wellcome Trust
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 111
Authors: 20
Affiliations: 3
Identifiers
Doi:
10.1073/pnas.0604283103
ISSN:
00278424
Research Areas
Genetics And Genomics
Study Design
Case-Control Study