Cell envelope maintenance by PhoP is essential formethylglyoxal resistance.

Duringinfections bacteria are engulfed by macrophages, a main line of defense against invading pathogens. Upon activation, macrophages increase glycolysis, producing the antibacterial aldehyde methylglyoxal. To test whether bacterial methylglyoxal resistance is required for robust infections, we sought to identifydefense mechanisms against methylglyoxal. We identifiedmutants were among the most highly sensitive strains to methylglyoxal in vitro.mutants are highly attenuated in mice but amutant was even more attenuated in mice that accumulate methylglyoxal. We further foundbacilli were more permeable to methylglyoxal and accumulated glycated proteins. Suppressor mutations in the fatty acid β-oxidation genesorrestored impermeability and resistance to methylglyoxal to amutant. Together, our data show that an important role for PhoP is to provideresistance to methylglyoxal toxicity in vivo by regulating cell envelope integrity.