A large self-transmissible plasmid from Nigeria confers resistance to multiple antibacterials without a carrying cost

Abstract

AbstractAntimicrobial resistance is rapidly expanding, in a large part due to mobile genetic elements. We screened 94 fecal fluoroquinolone-resistantEscherichia coliisolates from Nigeria for six plasmid-mediated quinolone resistance (PMQR) genes. Sixteen isolates harbored at least one of the PMQR genes and four were positive foraac-6-Ib-cr. In one strain,aac-6-Ib-crwas mapped to a 125 Kb self-transmissible IncFII plasmid, pMB2, which also bearsblaCTX-M-15, seven other functional resistance genes and multiple resistance pseudogenes. We hypothesized that pMB2 had been selected by antimicrobials and that its large size would confer a growth disadvantage. However, laboratory strains carrying pMB2 grew at least as fast as isogenic strains lacking the plasmid in both rich and minimal media. We excised a 32 Kb fragment containing thesitABCDand another putative transporter,pefB, apapBhomolog, and several open-reading frames of unknown function. The resulting 93 Kb mini-plasmid conferred slower growth rates and lower fitness than wildtype pMB2. Trans-complementing the deletion with the clonedsitABCDgenes confirmed that they accounted for the growth advantage conferred by pMB2 in iron-depleted media. The mini-plasmid additionally conferred autoaggregation and was less transmissible and both phenotypes could be complemented with apefBclone. pMB2 is a large plasmid with a flexible resistance region that contains multiple 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.