Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays a aA list of the 100 ORFs most highly induced by heat shock is provided as supplementary data with the online version of this paper (http://mic.sgmjournals.org).

TLDR

Heat‑shock protein regulation is crucial for Mycobacterium tuberculosis pathogenesis and involves genome‑wide transcriptional changes during stress. The study combined targeted mutagenesis with whole‑genome microarray profiling to identify transcription factors governing the major heat‑shock protein genes. Two regulons were defined: HspR represses the Hsp70 (DnaK) regulon and HrcA controls the Hsp60 (GroE) response, both overlapping with sigma‑factor‑mediated changes, and a novel HspR‑controlled α‑crystallin operon was discovered as a key heat‑shock gene.

Abstract

Regulation of the expression of heat-shock proteins plays an important role in the pathogenesis of Mycobacterium tuberculosis. The heat-shock response of bacteria involves genome-wide changes in gene expression. A combination of targeted mutagenesis and whole-genome expression profiling was used to characterize transcription factors responsible for control of genes encoding the major heat-shock proteins of M. tuberculosis. Two heat-shock regulons were identified. HspR acts as a transcriptional repressor for the members of the Hsp70 (DnaK) regulon, and HrcA similarly regulates the Hsp60 (GroE) response. These two specific repressor circuits overlap with broader transcriptional changes mediated by alternative sigma factors during exposure to high temperatures. Several previously undescribed heat-shock genes were identified as members of the HspR and HrcA regulons. A novel HspR-controlled operon encodes a member of the low-molecular-mass α-crystallin family. This protein is one of the most prominent features of the M. tuberculosis heat-shock response and is related to a major antigen induced in response to anaerobic stress.