The Heat Shock Response ofMycobacterium tuberculosis: Linking Gene Expression, Immunology and Pathogenesis

Abstract

The regulation of heat shock protein (HSP) expression is critically important to pathogens such asMycobacterium tuberculosisand dysregulation of the heat shock response results in increased immune recognition of the bacterium and reduced survival during chronic infection. In this study we use a whole genome spotted microarray to characterize the heat shock response ofM. tuberculosis. We also begin a dissection of this important stress response by generating deletion mutants that lack specific transcriptional regulators and examining their transcriptional profiles under different stresses. Understanding the stimuli and mechanisms that govern heat shock in mycobacteria will allow us to relate observedin vivoexpression patterns of HSPs to particular stresses and physiological conditions. The mechanisms controlling HSP expression also make attractive drug targets as part of a strategy designed to enhance immune recognition of the bacterium.