Abstract
Objectives: 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 mcr 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 Escherichia coli strains.Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli 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 E. coli strains.Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-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.Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli 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.
Highlights
The growing incidence of multidrug-resistant (MDR) bacteria is an unavoidable challenge in modern medicine
We report on the emergence of mcr-1.1-harboring IncX4 plasmid in six extraintestinal Escherichia coli strains of clinical origin isolated in University Hospital of Bialystok, Poland between 2016 and 2018
IncX4 Plasmids Phylogenomics For the purpose of IncX4 plasmid phylogenomic inference, 100 similar sequences from the BLAST database were aligned and Extraintestinal E. coli isolates incorporated into the described study presented a relatively similar antimicrobial resistance pattern (66.66%; 4 of 6)
Summary
The growing incidence of multidrug-resistant (MDR) bacteria is an unavoidable challenge in modern medicine. Referred to as polymyxin E, is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens, along with carbapenems and tigecycline (Livermore et al, 2011). Colistin was originally introduced in the 1950s for the treatment of infections caused by Gram-negative bacteria; polymyxins fell out of favor in the middle of the 1970s due to high rates of nephro- and neurotoxicity coupled with the advent of less toxic antibacterial agents. By the mid-1990s (El-Sayed Ahmed et al, 2020), polymyxins were reintroduced into clinical practice due to the emergence of extensively drug-resistant (XDR) Gram-negative bacteria, and currently serve a critical role in the antimicrobial armamentarium (Kaye et al, 2016). Bacterial resistance to polymyxin E emerged rapidly, and could potentially lead to essentially untreatable infections, in the hospital setting where aforementioned XDR microorganisms frequently cause lifethreatening infections in the most vulnerable patient populations (Kaye et al, 2016)
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