<b>Background</b> <p>The polymyxin antibiotic colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant and carbapenem-resistant Gram-negative bacteria. Mobile colistin resistance genes <i>mcr-9</i> and <i>mcr-10</i> are increasingly detected in Enterobacteriaceae but their epidemiology is poorly understood.</p> <b>Methods</b> <p>The genetic characteristics of <i>mcr-9</i> and <i>mcr-10</i>, being the only mobile colistin resistance genes detected in a local population of <i>Enterobacter</i> species isolated from bloodstream infections in Dartmouth Hitchcock Medical Center, USA, were elucidated and contextualized against a global dataset of <i>mcr-9/10-</i>bearing plasmids using genomic and phylogenetic tools.</p> <b>Results</b> <p>Seven out of 59 <i>Enterobacter</i> isolates carry either an <i>mcr</i><i>-9</i> or <i>mcr</i><i>-10</i> on a plasmid with distinct single and multiple replicon configurations, including IncFIB(pECLA), IncFIB(K), IncFIA(HI1)—IncFIB(K), IncFIB(pECLA)--IncFII(pECLA) and IncFIB(K)--IncFII(pECLA), whereas two genomes harbor <i>mcr</i><i>-9</i> on their chromosome. Global contextualization reveals that allelic variants of <i>mcr-9</i> and <i>mcr-10</i> are widely disseminated across diverse Inc-type plasmids, transcending geographic and taxonomic boundaries. Plasmid-borne genes conferring resistance to other antimicrobial agents, such as aminoglycoside, tetracycline and trimethoprim, tend to co-occur with <i>mcr-9.1</i> and <i>mcr-9.2</i> alleles.</p> <b>Conclusions</b> <p>Findings from this study enhance our understanding of the plasmid backgrounds of <i>mcr</i><i>-9</i> and <i>mcr</i><i>-10</i>, their associated antimicrobial resistance gene carriage and co-occurrence. This knowledge may be critical to inform scalable and effective public health interventions aimed at preserving the efficacy of colistin.</p>

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Dissemination dynamics of colistin resistance genes mcr-9 and mcr-10 across diverse Inc plasmid backbones

  • Odion O. Ikhimiukor,
  • Manuela Montoya-Giraldo,
  • Stephanie S. R. Souza,
  • Ifeoluwa J. Akintayo,
  • Nicole I. Zac Soligno,
  • Maitiú Marmion,
  • Elissa M. Eckhardt,
  • Nisalda Carreiro,
  • Adrienne A. Workman,
  • Isabella W. Martin,
  • Cheryl P. Andam

摘要

Background

The polymyxin antibiotic colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant and carbapenem-resistant Gram-negative bacteria. Mobile colistin resistance genes mcr-9 and mcr-10 are increasingly detected in Enterobacteriaceae but their epidemiology is poorly understood.

Methods

The genetic characteristics of mcr-9 and mcr-10, being the only mobile colistin resistance genes detected in a local population of Enterobacter species isolated from bloodstream infections in Dartmouth Hitchcock Medical Center, USA, were elucidated and contextualized against a global dataset of mcr-9/10-bearing plasmids using genomic and phylogenetic tools.

Results

Seven out of 59 Enterobacter isolates carry either an mcr-9 or mcr-10 on a plasmid with distinct single and multiple replicon configurations, including IncFIB(pECLA), IncFIB(K), IncFIA(HI1)—IncFIB(K), IncFIB(pECLA)--IncFII(pECLA) and IncFIB(K)--IncFII(pECLA), whereas two genomes harbor mcr-9 on their chromosome. Global contextualization reveals that allelic variants of mcr-9 and mcr-10 are widely disseminated across diverse Inc-type plasmids, transcending geographic and taxonomic boundaries. Plasmid-borne genes conferring resistance to other antimicrobial agents, such as aminoglycoside, tetracycline and trimethoprim, tend to co-occur with mcr-9.1 and mcr-9.2 alleles.

Conclusions

Findings from this study enhance our understanding of the plasmid backgrounds of mcr-9 and mcr-10, their associated antimicrobial resistance gene carriage and co-occurrence. This knowledge may be critical to inform scalable and effective public health interventions aimed at preserving the efficacy of colistin.