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

Abstract

Carbapenem-resistant Enterobacterales poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria via 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 Enterobacterales has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring blaOXA-181 in Enterobacterales is currently scarce. In this study, we aimed to determine the phylogeny and evolution of blaOXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring blaOXA-181 in Enterobacterales, we identified 81 blaOXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored blaOXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of blaOXA-181 among the 66 blaOXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring blaOXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in Escherichia coli and Klebsiella pneumoniae. Most of the IncX3 plasmids harboring blaOXA-181 were human origin. Almost all the blaOXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOBP 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 blaOXA-181 and qnrS1 in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS26 in the same orientation. Our findings provide important insights into the phylogeny and evolution of blaOXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading blaOXA-181 genes in Enterobacterales.

Plasmid genomic epidemiology of carbapenem-hydrolysing class D β-lactamase (CDHL)-producing Enterobacterales in Canada, 2010−2021

“…We examined SNV prevalence in two primary plasmid clusters whose plasmids were near identical (AA836, AB484). For IncX3/rep_cluster_1195 plasmids carrying bla OXA-181 (AA836), we found remarkably high conservation among plasmid sequences wherein many were 100 % identical to the reference sequence, agreeing with previous studies [ 8 15 69 73 74 ]. Although we found 1–3 SNVs in some plasmid sequences, these were scattered across the genome and did not appear to be linked to any epidemiological information which limits the usefulness of creating a Tn 2013 transposon typing scheme, as done for bla KPC genes with Tn 4401 [ 71 75 ].…”

A Whole-Genome Sequencing-Based Approach for the Characterization of Klebsiella pneumoniae Co-Producing KPC and OXA-48-like Carbapenemases Circulating in Sardinia, Italy

“…Eight isoforms (a to h) of Tn4401 have been identified so far, differing for deletions immediately upstream of the bla KPC gene, with Tn 4401 a and Tn 4401 b being the most common [ 61 ]. In our study, Tn 4401 a was identified in all strains carrying both the bla KPC-3 and bla KPC-31 genes, whereas ColKP3 and IncX3 are reported to be the main promoters involved in the spread of the bla OXA-181 and qnrS1 genes, conferring resistance to carbapenems and fluoroquinolones, respectively [ 62 ]. The presence of different AMR determinants within the same mobile elements highlights the genetic diversity of plasmids and their key role in the diffusion of AMR.…”