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The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis

Stewart, G. R, Newton, S. M, Wilkinson, K. A, Humphreys, Ian, Murphy, H. N, Robertson, B. D, Wilkinson, R. J and Young, D. B 2005. The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis. Molecular Microbiology 55 (4) , pp. 1127-1137. 10.1111/j.1365-2958.2004.04450.x

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Abstract

Mycobacterium tuberculosis has two members of the alpha-crystallin (Acr) family of molecular chaperones. Expression of Acr1 is induced by exposure to hypoxia or nitric oxide and is associated with bacterial persistence in a non-replicating state. Expression of Acr2 is induced by heat shock, oxidative stress, and uptake by macrophages. We have shown that Acr2 continues to be expressed at a high level during both acute and chronic infection in the mouse model, with an increased ratio of acr2:acr1 mRNA in the persistent phase. Deletion of the acr2 gene resulted in a decrease in the resistance of M. tuberculosis to oxidative stress but did not impair growth in mouse bone marrow macrophages. There was no difference in bacterial load in mice infected with an acr2 deletion mutant, but a marked alteration in disease progression was evident from reduced weight loss over a prolonged infection. This correlated with reduced recruitment of T-cells and macrophages to the lungs of mice infected with the acr2 mutant and reduced immune-related pathology. These findings demonstrate that both alpha-crystallins contribute to persistent infection with M. tuberculosis and suggest that manipulation of acr expression can influence the host response to infection

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Animals;Bacterial Proteins/metabolism*;Gene Deletion;Gene Expression Regulation;Hydrogen Peroxide/pharmacology;Lung/microbiology;Lung/pathology;Mice;Mycobacterium tuberculosis/classification;Mycobacterium tuberculosis/drug effects;Mycobacterium tuberculosis/genetics;Mycobacterium tuberculosis/pathogenicity*;Oxidative Stress;Phylogeny;RNA, Messenger/genetics;Tuberculosis/pathology;alpha-Crystallins/classification;alpha-Crystallins/genetics*;alpha-Crystallins/metabolism*;
Publisher: Wiley
ISSN: 0950-382X
Date of Acceptance: 25 October 2004
Last Modified: 05 Dec 2017 02:57
URI: http://orca.cf.ac.uk/id/eprint/107195

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