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The intestinal fatty acid propionate inhibits S almonella invasion through the post‐translational control of HilD
Author(s) -
Hung ChienChe,
Garner Cherilyn D.,
Slauch James M.,
Dwyer Zachary W.,
Lawhon Sara D.,
Frye Jonathan G.,
McClelland Michael,
Ahmer Brian M. M.,
Altier Craig
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12149
Subject(s) - biology , psychological repression , microbiology and biotechnology , mutant , intestinal epithelium , propionate , pathogenicity island , regulon , secretion , biochemistry , gene expression , gene , virulence , genetics , epithelium
Summary To cause disease, S almonella must invade the intestinal epithelium employing genes encoded within S almonella 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 S almonella in propionate significantly reduced the stability of HilD . Extending protein half‐life using a L on 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‐ C o A , while further metabolism of propionyl‐ C o A appeared not to be required. These results suggest a mechanism of control of S almonella virulence in which HilD is post‐translationally modified using the high‐energy intermediate propionyl‐ C o A .