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Negative regulation of Salmonella pathogenicity island 2 is required for contextual control of virulence during typhoid.


ABSTRACT: Salmonella enterica relies on a type III secretion system encoded in Salmonella pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control in vivo remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity island and established that this negative regulation is central to systemic pathogenesis because ydgT mutants overexpressing typhoid virulence genes were ultimately attenuated during infection. ydgT mutants displayed a biphasic virulence phenotype during in vivo competitive infections that consisted of an early "gain-of-virulence" dependent on SPI-2 activation, followed by attenuation later in infection indicating that proper contextual regulation of SPI-2 by YdgT is necessary for full virulence during systemic colonization. These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis in vivo.

SUBMITTER: Coombes BK 

PROVIDER: S-EPMC1297660 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

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Negative regulation of Salmonella pathogenicity island 2 is required for contextual control of virulence during typhoid.

Coombes Brian K BK   Wickham Mark E ME   Lowden Michael J MJ   Brown Nat F NF   Finlay B Brett BB  

Proceedings of the National Academy of Sciences of the United States of America 20051121 48


Salmonella enterica relies on a type III secretion system encoded in Salmonella pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control in vivo remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity  ...[more]

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