Comparative Analysis of Extended-Spectrum-β-Lactamase CTX-M-65-Producing Salmonella enterica Serovar Infantis Isolates from Humans, Food Animals, and Retail Chickens in the United States

We sequenced the genomes of 10 Salmonella enterica serovar Infantis isolates containing bla(CTX-M-65) obtained from chicken, cattle, and human sources collected between 2012 and 2015 in the United States through routine National Antimicrobial Resistance Monitoring System (NARMS) surveillance and product sampling programs. We also completely assembled the plasmids from four of the isolates. All isolates had a D87Y mutation in the gyrA gene and harbored between 7 and 10 resistance genes [aph(4)-Ia, aac(3)-IVa, aph(3')-Ic, bla(CTX-M-65), fosA3, floR, dfrA14, sul1, tetA, aadA1] located in two distinct sites of a megaplasmid (similar to 316 to 323 kb) similar to that described in a bla(CTX-M-65)-positive S. Infantis isolate from a patient in Italy. High-quality single nucleotide polymorphism (hqSNP) analysis revealed that all U.S. isolates were closely related, separated by only 1 to 38 pairwise high-quality SNPs, indicating a high likelihood that strains from humans, chickens, and cattle recently evolved from a common ancestor. The U.S. isolates were genetically similar to the bla(CTX-M-65)-positive S. Infantis isolate from Italy, with a separation of 34 to 47 SNPs. This is the first report of the bla(CTX-M-65) gene and the pESI (plasmid for emerging S. Infantis)-like megaplasmid from S. Infantis in the United States, and it illustrates the importance of applying a global One Health human and animal perspective to combat antimicrobial resistance.