Analysis of the Resistome of a Multidrug-Resistant NDM-1-Producing Escherichia coli Strain by High-Throughput Genome Sequencing

Abstract

ABSTRACTThe resistome of the multidrug-resistantEscherichia colistrain 271 carrying the plasmid-mediatedblaNDM-1carbapenemase gene was analyzed by high-throughput genome sequencing. The p271A plasmid carrying theblaNDM-1gene was 35.9 kb in size and possessed an IncN-type backbone that harbored a novel replicase gene. Acquisition of theblaNDM-1gene on plasmid p271A had been likely the result of a cointegration event involving the transposase of Tn5403. The expression ofblaNDM-1was associated with the insertion sequence ISAba125likely originating fromAcinetobacter baumannii. E. coli271 accumulated multiple resistance determinants, including five β-lactamase genes (comprising the extended-spectrum β-lactamase CTX-M-15), two 16S RNA methylase ArmA- and RmtB-encoding genes, and theqepAgene encoding an efflux pump involved in resistance to fluoroquinolones. These resistance genes were located on three additional plasmids, of 160 kb (IncA/C), 130 kb (IncF), and 110 kb (IncI1). In addition, several chromosomally encoded resistance determinants were identified, such as topoisomerase mutations, porin modifications and truncations, and the intrinsicampCgene ofE. colithat was weakly expressed. The multidrug resistance pattern observed forE. coli271 was therefore the result of combined chromosome- and plasmid-encoded mechanisms.