Dataset Information

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

ABSTRACT: Nontyphoidal Salmonella enterica (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 (n?=?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). 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 multistep approach that was validated by long-read sequencing. AARGs to quinolones [qnrB15, qnrB19, qnrB2, qnrD, qnrS1, qnrS2, and aac(6')Ib-cr] and ESC (bla CMY-2, bla CTX-M-1, bla CTX-M-27, and 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. enterica serovar Anatum from swine in the United States (GenBank accession number KY991369.1) and similar to Escherichia coli 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.

SUBMITTER: Elnekave E

PROVIDER: S-EPMC6437544 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Elnekave Ehud E Hong Samuel L SL Lim Seunghyun S Hayer Shivdeep S SS Boxrud Dave D Taylor Angela J AJ Lappi Victoria V Noyes Noelle N Johnson Timothy J TJ Rovira Albert A Davies Peter P Perez Andres A Alvarez Julio J

Antimicrobial agents and chemotherapy 20190327 4

Nontyphoidal Salmonella enterica (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 (n = 183) from U.S. swine clinical ca ...[more]

PMID: 30745386

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Project description:Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.

Dataset Information

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

Publications

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.

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