In silico characterization of IncX3 plasmids carrying blaOXA-181 in Enterobacterales

Abstract

Carbapenem-resistant <i>Enterobacterales</i> poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria <i>via</i> horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing <i>Enterobacterales</i> has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring <i>bla</i> _OXA-181 in <i>Enterobacterales</i> is currently scarce. In this study, we aimed to determine the phylogeny and evolution of <i>bla</i> _OXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring <i>bla</i> _OXA-181 in <i>Enterobacterales</i>, we identified 81 <i>bla</i> _OXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored <i>bla</i> _OXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of <i>bla</i> _OXA-181 among the 66 <i>bla</i> _OXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring <i>bla</i> _OXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>. Most of the IncX3 plasmids harboring <i>bla</i> _OXA-181 were human origin. Almost all the <i>bla</i> _OXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOB_P family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both <i>bla</i> _OXA-181 and <i>qnrS1</i> in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS<i>26</i> in the same orientation. Our findings provide important insights into the phylogeny and evolution of <i>bla</i> _OXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading <i>bla</i> _OXA-181 genes in <i>Enterobacterales</i>.