Fitness Advantage of mcr-1–Bearing IncI2 and IncX4 Plasmids in Vitro

Abstract

The objective of this study was to assess the impact of diverse plasmids bearing colistin resistance gene mcr-1 on host fitness. Forty-seven commensal E. coli isolates recovered from the pig farm where mcr-1 was first identified were screened for mcr-1. mcr-1-bearing plasmids were characterized by sequencing. The fitness impact of mcr-1-bearing plasmids was evaluated by in vitro competition assays. Twenty-seven (57.5%) E. coli isolates were positive for mcr-1. The mcr-1 genes were mainly located on plasmids belonging to IncI2 (n = 5), IncX4 (n = 11), IncHI2/ST3 (n = 8), IncFII (n = 2), and IncY (n = 2). InHI2 plasmids also carried other resistance genes (floR, blaCTX−M, and fosA3) and were only detected in isolates from nursery pigs. Sequences of the representative mcr-1–bearing plasmids were almost identical to those of the corresponding plasmid types reported previously. An increase in the fitness of IncI2- and IncX4-carrying strains was observed, while the presence of IncHI2, IncFII and IncY plasmids showed a fitness cost although an insignificant fitness increase was initially observed in IncFII or IncY plasmids-containing strains. Acquisition of IncI2-type plasmid was more beneficial for host E. coli DH5α than either IncHI2 or IncX4 plasmid, while transformants with IncHI2-type plasmid presented a competitive disadvantage against IncI2 or IncX4 plasmid containing strains. In conclusion, IncI2, IncX4, and IncHI2 were the major plasmid types driving the dissemination of mcr-1 in this farm. Increased fitness or co-selection by other antimicrobials might contribute to the further dissemination of the three epidemic mcr-1–positive plasmids (IncI2, IncX4, and IncHI2) in this farm and worldwide.

Whole Genome Sequencing and Characteristics of mcr-1–Harboring Plasmids of Porcine Escherichia coli Isolates Belonging to the High-Risk Clone O25b:H4-ST131 Clade B

“…However, because of the MDR profile of our ST131 isolates, this might not be that easy, due to coselection by other antimicrobials and host fitness adaptation. The fitness effects of carrying the mcr-1 gene were evaluated by Wu et al (2018). They proved that IncI2 and IncX4 mcr-1-positive plasmids conferred fitness advantage for its host.…”

Conjugal Transfer, Whole-Genome Sequencing, and Plasmid Analysis of Four mcr-1 -Bearing Isolates from U.S. Patients

“…Stability assays and WGS data demonstrated the pMCR-1-CT, pMCR-1-CTse, and pMCR-1-NY plasmids were stable and were nearly identical to each other as well as to other mcr-1-harboring IncX4 plasmids reported from multiple countries (15)(16)(17)(18)(19). The stability of the plasmids investigated here and the evidence of their international dissemination further support the idea that IncX4 plasmids may play a significant role in the spread of mcr-1 among Enterobacteriaceae (20)(21).…”

Applying Nanopore sequencing to a One-Health scenario for colistin resistance transmission among pigs, cows and the farmer

“…Plasmids encountered herein contained similar replicons to the ones described in the literature to be potential carriers of colistin resistance, with IncX4 being the most prevalent [50][51][52][53][54][55][56] . In agreement with other studies 51,[57][58][59] , some of the IncX4 plasmids have lost the transposition element ISApl1 involved in the mobilization of the mcr-1 gene suggesting its stabilization within the plasmid.…”

“…Additionally, the bovine isolate 15B-22 yielded mcr-1 in two different plasmids (IncHI2 and IncX4). Several studies have described coexistence of two mcr-1-harbouring plasmids within a host [52][53][54][55][56] or one copy on a plasmid and the other in the chromosome 53,55,56 .…”

“…As mentioned before, strains carrying mcr-1 in the genome have also been described previously 50,53,55,56 . Interestingly, in our study, mcr-1 was integrated in the genome in two isolates of different origin.…”