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

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.

SUBMITTER: Hung CC

PROVIDER: S-EPMC3581741 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Hung Chien-Che CC Garner Cherilyn D CD Slauch James M JM Dwyer Zachary W ZW Lawhon Sara D SD Frye Jonathan G JG McClelland Michael M Ahmer Brian M M BM Altier Craig C

Molecular microbiology 20130128 5

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 ...[more]

PMID: 23289537

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Project description:Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1-99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5-10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64-81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75-90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis.

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

Publications

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

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