In silico Evolution and Comparative Genomic Analysis of IncX3 Plasmids Isolated From China Over Ten Years

Abstract

IncX3 plasmids are correlated with the dissemination and acquisition of carbapenem resistance in Enterobacteriaceae and have been prevalent in China over the last 10 years. Since the distribution characteristics of IncX3 plasmids across China as well as their evolutionary traits for 10 years remain unclear, here we conducted a retrospective literature review and in silico comparative analysis of IncX3 plasmids in publicly available IncX3 plasmid genomes. IncX3 plasmids distributed in 17 provinces or cities were extracted for analysis, which tend to be specifically associated with hospital-isolated Escherichia coli ST410 from phylogroup A. Although the backbones of IncX3 plasmids have remained highly conservative over the last 10 years, the blaNDM resistance genetic contexts on these plasmids could fall into five subtypes, among which AR_N1_I has been identified in Enterobacter cloacae174 chromosome and AR_N5_I was simultaneously located on IncF and IncA/C plasmids. This suggests that the blaNDM resistance gene environment can spread between different plasmids, between different bacterial genera, or between strains and plasmids, highlighting that it is imperative to adopt more stringent infection control measures targeting IncX3 plasmid spread.

Global prevalence, characteristics, and future prospects of IncX3 plasmids: A review

“…The core genes are shared among the three typical completely sequenced IncX3 plasmids (pEC13_35, pIncX-SHV, and pNDM-HN380): replication (replication initiation protein, pir ; replication accessory protein, bis ), partitioning ( parA and parB ), plasmid maintenance (a putative DNA-binding protein, hns ; a putative type III topoisomerase, topB ), conjugation/type IV secretion system (T4SS, with 11 genes, pilX1 to pilX11 ), transcriptional activator ( actX ), and putative DNA transfer proteins ( taxA and taxC ) ( Ho et al, 2012 ). A retrospective analysis of IncX3 in China shows that the IncX3 plasmid backbone has been highly conserved over the past decade ( Liu et al, 2021a ). The accessory module mainly includes transposase genes, metabolic functions related genes, and antimicrobial resistance encoding genes.…”

Molecular Characterization of bla NDM -Carrying IncX3 Plasmids: bla NDM-16b Likely Emerged from a Mutation of bla NDM-5 on IncX3 Plasmid

“…In addition, other bla NDM variants carried on IncX3 plasmids, namely, bla NDM-17 , bla NDM-19 , bla NDM-20 , bla NDM-21 , and bla NDM-33 , have been reported ( 9 – 13 ). The role of the IncX3 plasmid in mediating the dissemination of bla NDM has therefore been considered ( 14 ).…”

Adaptive Evolution Compensated for the Plasmid Fitness Costs Brought by Specific Genetic Conflicts

“…However, there have been no studies on the relationship between specific genetic conflicts and the fitness cost of carrying ndm /IncX3 plasmids. Our work has previously revealed that the ndm /IncX3 plasmids are highly conserved [ 9 ], and thus we suggest that specific genetic conflicts that may occur in the host chromosome confer a diverse fitness cost.…”

“…However, some studies have also reported high fitness costs [ 12 , 13 ], though the variety of fitness costs and the mechanism involved remain unclear. Our group has been exploring IncX3 plasmid prevalence for several years [ 8 , 9 , 19 ]. In the present study, we found that the ndm /IncX3 plasmid led to an elevated fitness cost in the C600 strain, for which specific genetic conflicts were responsible and related to SNPs in genes of the cell membrane and sugar metabolism.…”

“…This cost in fitness has been attributed to plasmid properties, such as the number of copies, size of the plasmid, and related metabolic burden [ 4 , 5 , 6 , 7 ]. The ndm /IncX3 plasmid was considered to confer a low fitness cost because of its low copy number, minor metabolic burden, and stable genetic backbone [ 8 , 9 , 10 , 11 ]; however, high fitness costs have been reported in some E. coli strains [ 12 , 13 ]. The mechanism of the diversity of fitness costs while carrying the ndm /IncX3 plasmid remains unclear and is potentially unrelated to the general properties of the plasmid.…”