期刊
CELL HOST & MICROBE
卷 23, 期 1, 页码 65-+出版社
CELL PRESS
DOI: 10.1016/j.chom.2017.12.001
关键词
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资金
- Canadian Institutes of Health Research
- NIH [AI079022]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI079022, R01AI114618, R56AI079022] Funding Source: NIH RePORTER
Salmonella Typhi is the cause of typhoid fever, a major global health concern. An essential virulence factor of this pathogen is typhoid toxin. In contrast to most AB-type toxins, typhoid toxin is exclusively expressed by intracellular bacteria. The regulatory networks that ensure this unique gene expression pattern are unknown. Here, we developed FAST-INSeq, a genome-wide screening approach to identify S. Typhi genes required for typhoid toxin expression within infected cells. We find that typhoid toxin expression is controlled by a silencing and counter-silencing mechanism through the opposing actions of the PhoP/PhoQ two-component regulatory system and the histone-like protein H-NS. The screen also identified bacterial mutants that alter the proportion of intracellular S. Typhi that reside within an intravacuolar environment, which was essential for toxin expression. Collectively, these data describe a regulatory mechanism that allows a bacterial pathogen to exclusively express a virulence factor when located within a specific intracellular compartment.
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