Circulation of plasmids harboring resistance genes to quinolones and/or extended spectrum cephalosporins in multiple Salmonella enterica serotypes from swine in the United States [Mechanisms of Resistance]

Nontyphoidal Salmonella enterica (NTS) poses a major public-health risk worldwide that is amplified by the existence of antimicrobial resistant strains, especially to quinolones and extended-spectrum cephalosporins (ESC). Little is known on the dissemination of plasmids harboring the acquired genetic determinants that confer resistance to these antimicrobials across NTS serotypes from livestock in the United States.

NTS isolates (n=183) from U.S. swine clinical cases retrieved during 2014-2016 were selected for sequencing based on their phenotypic resistance to enrofloxacin (quinolone) or ceftiofur (3^rd-generation cephalosporin). De-novo assemblies were used to identify chromosomal mutations and acquired antimicrobial resistance genes (AARGs). In addition, plasmids harboring AARGs were identified using short-read assemblies and characterized using a multi-step approach that was validated by long-read sequencing.

AARGs to quinolones (qnrB15/qnrB19/qnrB2/qnrD/qnrS1/qnrS2/aac(6')Ib-cr) and ESC (bla_CMY-2/bla_CTX-M-1/bla_CTX-M-27/bla_SHV-12) were distributed across serotypes, and were harbored by several plasmids. In addition, chromosomal mutations associated with resistance to quinolones were identified in the target enzyme and efflux pump regulation genes. The predominant plasmid harboring the prevalent qnrB19 gene was distributed across serotypes. It was identical to a plasmid previously reported in S. Anatum from swine in the U.S. (KY991369.1), and similar to Escherichia coli plasmids from humans in South America (GQ374157.1 and JN979787.1). Our findings suggest that plasmids harboring AARGs to critically important antimicrobials are present in multiple NTS serotypes circulating in swine in the U.S. and can contribute to resistance expansion through horizontal transmission.

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