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Cell Host Microbe. 2018 Jan 10;23(1):65-76.e6. doi: 10.1016/j.chom.2017.12.001.

Decoding a Salmonella Typhi Regulatory Network that Controls Typhoid Toxin Expression within Human Cells.

Author information

1
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: jorge.galan@yale.edu.

Abstract

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.

KEYWORDS:

H-NS; PhoP/PhoQ; Salmonella Typhi pathogenesis; gene regulation; intracellular pathogens; typhoid toxin

PMID:
29324231
PMCID:
PMC5789772
DOI:
10.1016/j.chom.2017.12.001
[Indexed for MEDLINE]
Free PMC Article

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