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Infection and Immunity, April 2008, p. 1535-1546, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01078-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Mycobacterium tuberculosis Mutant Lacking the groEL Homologue cpn60.1 Is Viable but Fails To Induce an Inflammatory Response in Animal Models of Infection{triangledown}

Yanmin Hu,1 Brian Henderson,2 Peter A. Lund,3 Peter Tormay,1 M. Tabish Ahmed,3 Sudagar S. Gurcha,3 Gurdyal S. Besra,3 and Anthony R. M. Coates1*

Medical Microbiology, Centre of Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London SW17 ORE, United Kingdom,1 Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, London WC1X 8LD, United Kingdom,2 School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom3

Received 3 August 2007/ Returned for modification 12 September 2007/ Accepted 5 December 2007

The causative agent of tuberculosis, Mycobacterium tuberculosis, has two chaperonin (Cpn60) proteins and one cochaperonin (Cpn10) protein. We show here that cpn60.2 and cpn10, but not cpn60.1, are essential for cell survival. A mutant lacking Cpn60.1 was indistinguishable from the wild-type organism in plate and broth culture and within murine macrophages, although it showed increased sensitivity to high temperature (55°C). However, infection of mice with the {Delta}cpn60.1 mutant revealed a major difference from the wild-type organism. In spite of having equal numbers of bacteria in infected sites, the {Delta}cpn60.1 mutant failed to produce granulomatous inflammation in either mice or guinea pigs. This was associated with reduced cytokine expression in infected animals and macrophages. Cell wall lipid acid composition was not altered in the mutant strain. Thus, it appears that Cpn60.1 is an important agent in the regulation of the cytokine-dependent granulomatous response in M. tuberculosis infection.

* Corresponding author. Mailing address: Medical Microbiology, Centre of Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London SW17 ORE, United Kingdom. Phone: 44 (208) 725 5725. Fax: 44 (208) 672 0234. E-mail: acoates{at}sghms.ac.uk

{triangledown} Published ahead of print on 28 January 2008.

Editor: J. L. Flynn

Infection and Immunity, April 2008, p. 1535-1546, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01078-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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