A LOW PH-INDUCIBLE, PHOPQ-DEPENDENT ACID TOLERANCE RESPONSE PROTECTS SALMONELLA-TYPHIMURIUM AGAINST INORGANIC ACID STRESS

The acid tolerance response enables Salmonella typhimurium to survive exposures to potentially lethal acidic environments, The acid stress i mposed in a typical assay for acid tolerance (log-phase cells in minim al glucose medium) was shown to comprise both inorganic (i.e., low pH) and organic acid components. A gene previously determined to affect a cid tolerance, atbR, was identified as pgi, the gene encoding phosphog lucoisomerase. Mutations in pgi were shown to increase acid tolerance by preventing the synthesis of organic acids. Protocols designed to se parate the stresses of inorganic from organic acids revealed that the regulators sigma(38) (RpoS), Furl and Ada have major effects on tolera nce to organic acid stress but only minor effects on inorganic acid st ress. In contrast, the two-component regulatory system PhoP (identifie d as acid shock protein ASP29) and PhoQ proved to be important for tol erance to organic acid stress but had little effect against organic ac id stress, PhoP mutants also failed to induce four ASPs, confirming a role for this regulator in acid tolerance. Acid shock induction of Pho P appears to occur at the transcriptional le, el and requires the PhoP Q system. Furthermore, induction by acid occurs even in the presence o f high concentrations of magnesium, the ion known to be sensed by PhoQ , These results suggest that PhoQ can sense both Mg2+ and pH, Since ph oP mutants are avirulent, the low pH activation of this system has imp ortant implications concerning the pathogenesis of S. typhimurium. The involvement of four regulators, two of which are implicated in virule nce, underscores the complexity of the acid tolerance stress response aid further suggests that features of acid tolerance and virulence are interwoven.