Abstract
The role of plasmids in the complex pandemic of antimicrobial resistance is increasingly being recognized. In this respect, multiple mobile colistin resistance (mcr) gene-carrying plasmids have been described. However, the characteristics and epidemiology of these plasmids within local healthcare settings are largely unknown. We retrospectively characterized the genetic composition and epidemiology of plasmids from mcr-1-positive bacterial isolates identified from patients from a large academic hospital in the Netherlands. Clinical Gram-negative bacteria with an MIC > 2 μg/mL for colistin, obtained from patients hospitalized at the Erasmus MC University Medical Center Rotterdam during the years 2010–2018, were screened for presence of the mcr-1 gene. Extracted plasmids from mcr-1-positive isolates were sequenced using a combination of short- and long-read sequencing platforms, characterized by incompatibility type and genetic composition and compared to publicly available mcr-1-carrying plasmid sequences. In 21 isolates from 14 patients, mcr-1 was located on a plasmid. These plasmids were of diverse genetic background involving Inc types IncX4, IncI2(delta), IncHI2, as well as double Inc types IncHI2/IncN and IncHI2/IncQ. mcr-1-carrying plasmids were found in Escherichia coli, Klebsiella pneumoniae, and Kluyvera georgiana, and within the chromosome of an ST147 K. pneumoniae isolate. In depth analysis indicated intrapatient, interpatient, and interspecies transmission events of mcr-1-carrying plasmids. In addition, our results show that the mcr-1 gene resides in a rich environment full of other (mcr-1 negative) plasmids and of many different Inc types, enabling interplasmidal transfer events and facilitating widespread dissemination of the mcr-1 gene. Multiple mcr-1-carrying plasmid transmission events had likely occurred among isolates from hospitalized patients. Recognition and identification of plasmid transmission events within hospitals is necessary in order to design and implement effective infection control measures.
Highlights
The plasmid-mediated mobile colistin resistance gene was first reported in 2015 and has been detected across all continents (Liu et al, 2016; Wang R. et al, 2018; Elbediwi et al, 2019)
Mcr genes have been detected in plasmids of diverse incompatibility (Inc) types, with IncI2, IncHI2, and InX4 being the most abundant types identified (Matamoros et al, 2017)
Plasmids carrying the mcr-1 gene have been mainly described in Escherichia coli and Klebsiella pneumoniae (Terveer et al, 2017; Wang et al, 2017), but have been identified in other Enterobacterales (Tse and Yuen, 2016; Caselli et al, 2018)
Summary
The plasmid-mediated mobile colistin resistance gene (mcr-1) was first reported in 2015 and has been detected across all continents (Liu et al, 2016; Wang R. et al, 2018; Elbediwi et al, 2019). The location of mcr-1 within plasmids contributes to the gene’s mobility via horizontal transfer, allowing the spread of colistin resistance between different bacterial species. This phenomenon has been observed in livestock and more recently in healthcare settings (Carattoli, 2013; Liu et al, 2016; Shen et al, 2018; Wang X. et al, 2018). Nosocomial spread of the mcr-1 gene or mcr-1containing plasmids has been rarely reported (Mendes et al, 2018; Mariani et al, 2020) This may be due to the current limited use of plasmid detection and characterization for hospital epidemiology and infection prevention and control purposes
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