Investigating the Impact of Acid Adaptation on Cross-Protection in Salmonella Typhimurium and Its Regulatory...

This study investigated whether the slightly acidic environment in the meat industry activates the Salmonella PmrA/B two-component regulatory system (TCS), thereby enhancing acid tolerance and cross-protection, by constructing a mutant strain lacking the response regulator PmrA. Results showed that deletion of pmrA not only reduced the acid tolerance induced by S. Typhimurium at pH 5.4 (the ultimate pH for beef cattle after slaughter) but also further reduced its cross-stress resistance to heat (55 °C), osmotic (8% NaCl), oxidative (5 mM H₂O₂), and most (but not all) antibiotics. Transcriptomics data revealed that down-regulation of genes mediating lipopolysaccharide modification and peptidoglycan synthesis led to reduced resistance to cationic antimicrobial peptides. Down-regulation of glycerophospholipid and lysine metabolic pathways, together with limited activation of genes in the glutathione metabolism pathway in the ΔpmrA mutant, was associated with reduced cross-resistance to osmotic, acid, and oxidative stresses. Furthermore, the down-regulation of several TCS genes related to envelope modification and the electron respiratory chain may have further impaired Salmonella cross-stress resistance and intestinal colonization. These findings highlight the critical role of PmrA/B TCS in Salmonella cross-protection and provide mechanistic insights for controlling pathogen persistence in meat processing environments.