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ClgR regulation of chaperone and protease systems is essential for Mycobacterium tuberculosis parasitism of the macrophage

Estorninho, M, Smith, H, Thole, J, Harders-Westerveen, J, Kierzek, A, Butler, RE, Neyrolles, O and Stewart, GR (2010) ClgR regulation of chaperone and protease systems is essential for Mycobacterium tuberculosis parasitism of the macrophage Microbiology, 156 (11). 3445 - 3455. ISSN 1350-0872

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Abstract

Chaperone and protease systems play essential roles in cellular homeostasis and have vital functions in controlling the abundance of specific cellular proteins involved in processes such as transcription, replication, metabolism and virulence. Bacteria have evolved accurate regulatory systems to control the expression and function of chaperones and potentially destructive proteases. Here, we have used a combination of transcriptomics, proteomics and targeted mutagenesis to reveal that the clp gene regulator (ClgR) of Mycobacterium tuberculosis activates the transcription of at least ten genes, including four that encode protease systems (ClpP1/C, ClpP2/C, PtrB and HtrA-like protease Rv1043c) and three that encode chaperones (Acr2, ClpB and the chaperonin Rv3269). Thus, M. tuberculosis ClgR controls a larger network of protein homeostatic and regulatory systems than ClgR in any other bacterium studied to date. We demonstrate that ClgR-regulated transcriptional activation of these systems is essential for M. tuberculosis to replicate in macrophages. Furthermore, we observe that this defect is manifest early in infection, as M. tuberculosis lacking ClgR is deficient in the ability to control phagosome pH 1 h post-phagocytosis.

Item Type: Article
Additional Information: This work was supported by the European Community (TB-MACS, grant no. LSHP-CT-2006-037732) and by a University of Surrey studentship, awarded to M. E. We thank the  μG@S at St Georges Hospital Medical School for the supply of and assistance with microarrays.
Uncontrolled Keywords: GRAM-POSITIVE BACTERIA, SIGMA-FACTOR SIGMA(H), HEAT-SHOCK RESPONSE, ALPHA-CRYSTALLIN, CORYNEBACTERIUM-GLUTAMICUM, BACILLUS-SUBTILIS, GENE-EXPRESSION, MICROARRAY DATA, QUALITY-CONTROL, CLP ATPASES
Divisions: Faculty of Health and Medical Sciences > Microbial and Cellular Sciences
Depositing User: Symplectic Elements
Date Deposited: 29 Mar 2012 08:57
Last Modified: 23 Sep 2013 19:06
URI: http://epubs.surrey.ac.uk/id/eprint/184922

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