Carbapenem resistance in extensively drug-resistant Salmonella enterica serovar Agona and AmpC β-lactamase-producing S. Infantis

Abstract

ABSTRACT We report that carbapenem resistance developed in an extensively drug-resistant Salmonella enterica serovar Agona strain during antimicrobial therapy and in an AmpC β-lactamase-producing S . Infantis strain. Whole-genome sequence analysis indicated that carbapenem resistance in the S . Agona strain was associated with the insertion of a 160-kb IS15DI composite transposon in ompC_378 , which encodes a porin consisting of 378 amino acids, along with a 397-bp deletion in the ompD . The transposon harbored 12 resistance genes including bla CTX-M-55 and an efflux pump regulatory gene, ramAp . Carbapenem resistance in the bla CMY-2 -carrying S . Infantis strain was linked to the insertion of a 22,905-bp segment located 10 bp upstream of the ompC_378 coding sequence, as well as a 254-bp deletion in ompD . Our findings indicate that the loss of both ompC_378 and ompD is necessary for carbapenem resistance in extended-spectrum β-lactamase and AmpC β-lactamase-producing Salmonella strains. IMPORTANCE Carbapenem resistance arising from the loss of porins is commonly observed in extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producing strains of certain Enterobacteriaceae genera, including Klebsiella pneumoniae , Escherichia coli , and Pseudomonas aeruginosa . However, this resistance mechanism is rarely reported in the Salmonella genus. To address this knowledge gap, our study offers genetic evidence demonstrating that the loss of two specific porins (OmpC_378 and OmpD) is crucial for the development of carbapenem resistance in Salmonella ESBL and AmpC β-lactamase-producing strains. Furthermore, our findings reveal that most Salmonella serovars carry seven porin parathologs, with OmpC_378 and OmpD being the key porins involved in the development of carbapenem resistance in Salmonella strains.