AUTHOR=Majewski Piotr , Gutowska Anna , Smith David G. E. , Hauschild Tomasz , Majewska Paulina , Hryszko Tomasz , Gizycka Dominika , Kedra Boguslaw , Kochanowicz Jan , Glowiński Jerzy , Drewnowska Justyna , Swiecicka Izabela , Sacha Pawel T. , Wieczorek Piotr , Iwaniuk Dominika , Sulewska Anetta , Charkiewicz Radoslaw , Makarewicz Katarzyna , Zebrowska Agnieszka , Czaban Slawomir , Radziwon Piotr , Niklinski Jacek , Tryniszewska Elzbieta A. 

TITLE=Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.547020

DOI=10.3389/fmicb.2021.547020

ISSN=1664-302X

ABSTRACT=<p><bold>Objectives:</bold> The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne <italic>mcr</italic> colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal <italic>Escherichia coli</italic> strains.</p><p><bold>Methods:</bold> Molecular investigation of colistin-resistance was performed in six extraintestinal <italic>E. coli</italic> strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical <italic>E. coli</italic> strains.</p><p><bold>Results:</bold> Here we report on the emergence of six <italic>mcr</italic>-1.1-producing extraintestinal <italic>E. coli</italic> isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, <italic>mcr-</italic>1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene.</p><p><bold>Conclusion:</bold> IncX4 <italic>mcr-</italic>containing plasmids are reported as increasingly disseminated among <italic>E. coli</italic> isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different <italic>E. coli</italic> clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.</p>