Acetate uptake alleviates propionate-mediated growth restriction in <i>Yersinia enterocolitica</i>

. Propionate exerted the most potent toxicity by both pH-dependent and pH-independent mechanisms. pH-dependent propionate growth restriction was worsened in a mutant lacking ornithine decarboxylase, suggesting that this enzyme is involved in counteracting cytoplasmic acidification by propionate under acidic environmental conditions. pH-independent propionate toxicity required phosphate acetyltransferase (phosphotransacetylase) and acetate kinase, pointing to conversion of intracellular propionate to toxic propionyl-CoA by promiscuous phosphotransacetylase and acetate kinase activities as a mechanism of propionate toxicity. We also found that pH-independent propionate toxicity was alleviated by exogenous acetate, taken up via the acetate/succinate transporter SatP. This work advances our understanding of how short-chain fatty acids restrict pathogen growth and highlights strategies used by bona fide pathogens to overcome short-chain fatty acid-mediated colonization resistance.