Biological cost of AmpC production for Salmonella enterica serotype Typhimurium

Chromosomally mediated AmpC-type beta-lactamases are frequently found among Enterobacteriaceae. Hyperproduction of AmpC beta-lactamase results in high-level resistance to beta-lactam antibiotics. One striking feature of Salmonella is the absence of the structural ampC gene, encoding AmpC beta-lactamase, in contrast with other members in the Enterobacteriaceae family, such as Escherichia, Citrobacter, or Enterobacter. The horizontal acquisition of ampC genes is one of the causes of the increased resistance to extended-spectrum cephalosporins and beta-lactamase inhibitors among gram-negative rods. Nevertheless, despite the high number of beta-lactam-resistant Salmonella isolates so far described, only two strains expressing resistance to cephalosporin and beta-lactamase inhibitors which is mediated by AmpC-type enzymes have been found. In this work, data are provided which support the possibility that the maintenance and expression of the ampC gene may represent an unbearable cost for Salmonella in terms of reduction of some of its lifestyle attributes, such as growth rate and invasiveness. The deleterious AmpC burden can be eliminated by decreasing the production of AmpC when both the regulatory gene, ampR, and ampC are present in Salmonella. Thus, it is suggested that the two genes have to be acquired together by Salmonella, leading to an inducible beta-lactam resistance phenotype. AmpC synthesis did not produce major variations in the peptidoglycan composition of Salmonella.