β-Lactam resistance in enteric bacteria is frequently caused by mutations inampDencoding a cytosolicN-acetylmuramyl-l-alanine amidase. Such mutants are blocked in murein (peptidoglycan) recycling and accumulate cytoplasmic muropeptides that interact with the transcriptional activatorampR,which de-repressesβ-lactamase expression.Salmonella entericaserovar Typhimurium,an extensively studied enteric pathogen, was used to show that mutations inampDdecreased the ability ofS. typhimuriumto enter a macrophage derived cell line and made the bacteria more potent as inducers of inducible nitric oxide synthase (iNOS), as compared with the wild-type.ampGmutants, defective in the transport of recycled muropeptides across the cytoplasmic membrane, behaved essentially as the wild-type in invasion assays and in activation of iNOS. AsampDmutants also have reducedin vivofitness in a murine model, we suggest that the cytoplasmic accumulation of muropeptides affects the virulence of theampDmutants. [ABSTRACT FROM AUTHOR]