The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD

Chien Che Hung, Cherilyn D. Garner, James M. Slauch, Zachary W. Dwyer, Sara D. Lawhon, Jonathan G. Frye, Michael Mcclelland, Brian M M Ahmer, Craig Altier

Research output: Contribution to journalArticle

Abstract

To cause disease, Salmonella must invade the intestinal epithelium employing genes encoded within Salmonella Pathogenicity Island 1 (SPI1). We show here that propionate, a fatty acid abundant in the intestine of animals, repressed SPI1 at physiologically relevant concentration and pH, reducing expression of SPI1 transcriptional regulators and consequently decreasing expression and secretion of effector proteins, leading to reduced bacterial penetration of cultured epithelial cells. Essential to repression was hilD, which occupies the apex of the regulatory cascade within SPI1, as loss of only this gene among those of the regulon prevented repression of SPI1 transcription by propionate. Regulation through hilD, however, was achieved through the control of neither transcription nor translation. Instead, growth of Salmonella in propionate significantly reduced the stability of HilD. Extending protein half-life using a Lon protease mutant demonstrated that protein stability itself did not dictate the effects of propionate and suggested modification of HilD with subsequent degradation as the means of action. Furthermore, repression was significantly lessened in a mutant unable to produce propionyl-CoA, while further metabolism of propionyl-CoA appeared not to be required. These results suggest a mechanism of control of Salmonella virulence in which HilD is post-translationally modified using the high-energy intermediate propionyl-CoA.

Original languageEnglish (US)
Pages (from-to)1045-1060
Number of pages16
JournalMolecular Microbiology
Volume87
Issue number5
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Hung, C. C., Garner, C. D., Slauch, J. M., Dwyer, Z. W., Lawhon, S. D., Frye, J. G., Mcclelland, M., Ahmer, B. M. M., & Altier, C. (2013). The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD. Molecular Microbiology, 87(5), 1045-1060. https://doi.org/10.1111/mmi.12149