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Nature. 2008 Aug 7;454(7205):717-21. doi: 10.1038/nature07219.

Secreted transcription factor controls Mycobacterium tuberculosis virulence.

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  • 1Department of Microbiology and Immunology, Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, California 94143-2200, USA.

Abstract

Bacterial pathogens trigger specialized virulence factor secretion systems on encountering host cells. The ESX-1 protein secretion system of Mycobacterium tuberculosis-the causative agent of the human disease tuberculosis-delivers bacterial proteins into host cells during infection and is critical for virulence, but how it is regulated is unknown. Here we show that EspR (also known as Rv3849) is a key regulator of ESX-1 that is required for secretion and virulence in mice. EspR activates transcription of an operon that includes three ESX-1 components, Rv3616c-Rv3614c, whose expression in turn promotes secretion of ESX-1 substrates. EspR directly binds to and activates the Rv3616c-Rv3614c promoter and, unexpectedly, is itself secreted from the bacterial cell by the ESX-1 system that it regulates. Efflux of the DNA-binding regulator results in reduced Rv3616c-Rv3614c transcription, and thus reduced ESX-1 secretion. Our results reveal a direct negative feedback loop that regulates the activity of a secretion system essential for virulence. As the virulence factors secreted by the ESX-1 system are highly antigenic, fine control of secretion may be critical to successful infection.

Comment in

PMID:
18685700
[PubMed - indexed for MEDLINE]
PMCID:
PMC2862998
Free PMC Article

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