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

Decoding a Salmonella Typhi Regulatory Network that Controls Typhoid Toxin Expression within Human Cells.
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DOI:
10.1016/j.chom.2017.12.001
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发表时间:
2018-01-10
影响因子:
30.3
通讯作者:
Galán JE
Galán JE
中科院分区:
医学1区
文献类型:
--
作者:
Fowler CC;Galán JE

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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 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. Typhoid toxin, a central Salmonella Typhi virulence factor, is an unusual AB-type toxin in that it is exclusively expressed by intracellular bacteria. Here, Fowler & Galán develop a genetic screen and unveil the regulatory mechanisms that control typhoid toxin intracellular expression. Toxin expression requires bacterial localization within Salmonella containing vacuoles
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