Circulation of Plasmids Harboring Resistance Genes to Quinolones and/or Extended-Spectrum Cephalosporins in Multiple <i>Salmonella enterica</i> Serotypes from Swine in the United States

Abstract

Nontyphoidal <i>Salmonella enterica</i> (NTS) poses a major public health risk worldwide that is amplified by the existence of antimicrobial-resistant strains, especially those resistant 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 (<i>n</i> = 183) from U.S. swine clinical cases retrieved during 2014 to 2016 were selected for sequencing based on their phenotypic resistance to enrofloxacin (quinolone) or ceftiofur (3rd-generation cephalosporin). <i>De novo</i> 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 multistep approach that was validated by long-read sequencing. AARGs to quinolones [<i>qnrB15</i>, <i>qnrB19</i>, <i>qnrB2</i>, <i>qnrD</i>, <i>qnrS1</i>, <i>qnrS2</i>, and <i>aac(6')Ib-cr</i>] and ESC (<i>bla</i>_CMY-2, <i>bla</i>_CTX-M-1, <i>bla</i>_CTX-M-27, and <i>bla</i>_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 <i>qnrB19</i> gene was distributed across serotypes. It was identical to a plasmid previously reported in <i>S. enterica</i> serovar Anatum from swine in the United States (GenBank accession number KY991369.1) and similar to <i>Escherichia coli</i> plasmids from humans in South America (GenBank accession numbers GQ374157.1 and JN979787.1). Our findings suggest that plasmids harboring AARGs encoding mechanisms of resistance to critically important antimicrobials are present in multiple NTS serotypes circulating in swine in the United States and can contribute to resistance expansion through horizontal transmission.