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

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.

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

“…The distribution and genetic identification of resistance genes among individual plasmid types across different bacterial strains have been documented ( Venturini et al, 2013 ; Carattoli et al, 2015 ; Reid et al, 2015 ; Seiffert et al, 2017 ; Moran and Hall, 2019 ; Chang et al, 2020 ; Majewski et al, 2021 ). In the current study, we applied several bioinformatic tools including BLAST, AMRFinderPlus, and ISFinder for detecting genes in assembled plasmid sequence data and assessed the combination of resistance genes and MGEs, and individual plasmid types from enteric bacterial species to better elucidate AMR epidemiology as an effort to respond to this important public health threat.…”

Sheep and goats are reservoirs of colistin resistant Escherichia coli that co‐resist critically important antimicrobials: First study from Jordan

“…The co-resistance of mcr-1 colistin-resistance E. coli to β-lactams, fluoroquinolone, aminoglycoside, folate pathway antagonist was also reported in clinical E. coli strains in Poland (Majewski et al, 2021), and…”

Heterogeneous efflux pump expression underpins phenotypic resistance to antimicrobial peptides

“…Subsequently, we tested whether this newly observed bimodal distribution of tachyplesin-NBD accumulation was unique to the E. coli BW25113 strain. We found that the bimodal distribution in single-cell fluorescence was also present in nine E. coli clinical isolates (treated with tachyplesin-NBD at 46 μg mL -1 for 60 min) characterised by a diverse genetic background and various antimicrobial resistance genes, such as the polymyxin-E resistance gene mcr1 38 (Figure 1B, 1C and Data Set S1). The low accumulator median in strains JD1147 and MC04960 were shifted to the left and to the right, respectively, compared to BW25113, whereas the high accumulator median in the distribution for strain JS1060 was shifted to the left compared to BW25113.…”