Abstract
In this study, we aim to characterize the genetic environment of the plasmid-mediated colistin resistance gene mcr-1 in 25 Escherichia coli and seven Klebsiella pneumoniae strains from different countries and continents. Multilocus sequence typing, conjugation experiments, plasmid typing, and the presence and location of the insertion sequence ISApl1 were investigated. Whole genome sequencing of four E. coli was performed to analyse the genetic environment of the mcr-1 gene. Colistin minimum inhibitory concentration of mcr-1 strains varied from 3 to 32 µg/mL. Six E. coli sequence types were detected: ST 4015, ST 3997, ST 10, ST 93, ST 48, and ST 648. IncHI2, IncI2, and IncP plasmid types were predominant and were unrelated to a specific country of origin. ISApl1 was found in 69% of analysed plasmids that were mainly around the mcr-1 gene. Analysis of four closed mcr-1 plasmids revealed the integration of mcr-1 into hotspots. We found that the spread of mcr-1 gene was due to the diffusion of a composite transposon and not to the diffusion of a specific plasmid or a specific bacterial clone. The ease with which the mcr-1 gene integrates into various regions facilitates its dissemination among bacteria and explains its large diffusion all over the world, both in animals and in humans.
Highlights
Antibiotic resistance is a major issue around the world.This phenomenon has led clinicians to adapt treatment strategies and to use powerful, broad spectrum antibiotics, such as carbapenems against multi drug resistant Gram-negative bacteria
Different clones were identified with seven different sequence types (STs) in K. pneumoniae strains and 17 different STs in E. coli strains, including six recurrent STs, namely ST 4015, ST 3997, ST
Following the subculture of strains, the loss of the mcr-1 gene was observed in four K. pneumoniae strains after 25 passages
Summary
Antibiotic resistance is a major issue around the world. This phenomenon has led clinicians to adapt treatment strategies and to use powerful, broad spectrum antibiotics, such as carbapenems against multi drug resistant Gram-negative bacteria. The recent emergence of carbapenemase-producing bacteria around the world [1] has obliged clinicians to turn, as a last resort, to colistin [2,3]. A transferable colistin resistance mechanism, due to the presence of mcr-1 genes and variants that code for a phosphoethanolamine transferase, which have been detected in all continents [5] on a plasmid, has been described [6,7,8,9,10,11]. The mcr-1 gene has been described as being associated with an open reading frame (ORF), encoding a protein that is similar to a PAP2 superfamily protein, following the mcr-1 gene with an insertion
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