Secreted transcription factor controls Mycobacterium tuberculosis virulence

Article

关键词: BACILLUS-CALMETTE-GUERIN;    PSEUDOMONAS-AERUGINOSA;    ESAT-6 SECRETION;    GENE-EXPRESSION;    SYSTEM;    INFECTION;    ANTIGEN;    PROTEIN;    MACROPHAGES;    VACCINATION;   

DOI  :  10.1038/nature07219

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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