Biological Cost of AmpC Production for Salmonella enterica Serotype Typhimurium

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Abstract
Chromosomally mediated AmpC-type β-lactamases are frequently found among Enterobacteriaceae. Hyperproduction of AmpC β-lactamase results in high-level resistance to β-lactam antibiotics. One striking feature of Salmonella is the absence of the structural ampC gene, encoding AmpC β-lactamase, in contrast with other members in theEnterobacteriaceae 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 β-lactamase inhibitors among gram-negative rods. Nevertheless, despite the high number of β-lactam-resistant Salmonellaisolates so far described, only two strains expressing resistance to cephalosporin and β-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 forSalmonella 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 β-lactam resistance phenotype. AmpC synthesis did not produce major variations in the peptidoglycan composition ofSalmonella.