4.7 Article

A large self-transmissible resistance plasmid from Nigeria contains genes that ameliorate a carrying cost

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SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-019-56064-z

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  1. UK Medical Research Council (MRC) under the MRC/DFID Concordat agreement, part of the EDCTP2 program - European Union
  2. UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, part of the EDCTP2 program - European Union
  3. Branco Weiss Fellowship from the Society in Science, Zurich, Switzerland
  4. US National Science Foundation 'Research at Undergraduate Institutions' award [MCB 0948460]
  5. Haverford College, PA, USA
  6. American Society for Microbiology
  7. MRC [MR/L00464X/1] Funding Source: UKRI

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Antimicrobial resistance is rapidly expanding, in a large part due to mobile genetic elements. We screened 94 fecal fluoroquinolone-resistant Escherichia coli isolates from Nigeria for six plasmid-mediated quinolone resistance (PMQR) genes. Sixteen isolates harbored at least one of the PMQR genes and four were positive for aac-6-Ib-cr. In one strain, aac-6-Ib-cr was mapped to a 125 Kb self-transmissible IncFII plasmid, pMB2, which also bears bla(CTX-M-15), seven other functional resistance genes and multiple resistance pseudogenes. Laboratory strains carrying pMB2 grew faster than isogenic strains lacking the plasmid in both rich and minimal media. We excised a 32 Kb fragment containing transporter genes and several open-reading frames of unknown function. The resulting 93 Kb miniplasmid conferred slower growth rates and lower fitness than wildtype pMB2. Trans-complementing the deletion with the cloned sitABCD genes confirmed that they accounted for the growth advantage conferred by pMB2 in iron-depleted media. pMB2 is a large plasmid with a flexible resistance region that contains loci that can account for evolutionary success in the absence of antimicrobials. Ancillary functions conferred by resistance plasmids can mediate their retention and transmissibility, worsening the trajectory for antimicrobial resistance and potentially circumventing efforts to contain resistance through restricted use.

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