How to: screening for mcr-mediated resistance to colistin

Smelikova, Eva; Tkadlec, Jan; Krutova, Marcela

doi:10.1016/j.cmi.2021.09.009

Cited by 17 publications

(13 citation statements)

References 61 publications

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“…Thus, future investigations on the distribution of the remaining mcr genes among the strain collection would be preferable. The chosen laboratory method since 2018, i.e., selective culturing of isolates on sheep blood agar containing 4 mg/L colistin, may have led to a fewer detection rate of mcrpositive isolates with low or diminished growth rates under these conditions (Smelikova et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Occurrence of mcr-1 and mcr-2 colistin resistance genes in porcine Escherichia coli isolates (2010–2020) and genomic characterization of mcr-2-positive E. coli

et al. 2022

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IntroductionThe global emergence of plasmid-mediated colistin resistance is threatening the efficacy of colistin as one of the last treatment options against multi-drug resistant Gram-negative bacteria. To date, ten mcr-genes (mcr-1 to mcr-10) were reported. While mcr-1 has disseminated globally, the occurrence of mcr-2 was reported scarcely.Methods and resultsWe determined the occurrence of mcr-1 and mcr-2 genes among Escherichia coli isolates from swine and performed detailed genomic characterization of mcr-2-positive strains. In the years 2010-2017, 7,614 porcine E. coli isolates were obtained from fecal swine samples in Europe and isolates carrying at least one of the virulence associated genes predicting Shiga toxin producing E. coli (STEC), enterotoxigenic E. coli (ETEC) or enteropathogenic E. coli (EPEC) were stored. 793 (10.4%) of these isolates carried the mcr-1 gene. Of 1,477 additional E. coli isolates obtained from sheep blood agar containing 4 mg/L colistin between 2018 and 2020, 36 (2.4%) isolates were mcr-1-positive. In contrast to mcr-1, the mcr-2 gene occurred at a very low frequency (0.13%) among the overall 9,091 isolates. Most mcr-2-positive isolates originated from Belgium (n = 9), one from Spain and two from Germany. They were obtained from six different farms and revealed multilocus sequence types ST10, ST29, ST93, ST100, ST3057 and ST5786. While the originally described mcr-2.1 was predominant, we also detected a new mcr-2 variant in two isolates from Belgium, which was termed mcr-2.8. MCR-2 isolates were mostly classified as ETEC or ETEC-like, while one isolate from Spain represented an atypical enteropathogenic E. coli (aEPEC; eae+). The ST29-aEPEC isolate carried mcr-2 on the chromosome. Another eight isolates carried their mcr-2 gene on IncX4 plasmids that resembled the pKP37-BE MCR-2 plasmid originally described in Belgium in 2015. Three ST100 E. coli isolates from a single farm in Belgium carried the mcr-2.1 gene on a 47-kb self-transmissible IncP type plasmid of a new IncP-1 clade.DiscussionThis is the first report of mcr-2 genes in E. coli isolates from Germany. The detection of a new mcr-2 allele and a novel plasmid backbone suggests the presence of so far undetected mcr-2 variants and mobilizable vehicles.

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Section: Discussionmentioning

confidence: 99%

Occurrence of mcr-1 and mcr-2 colistin resistance genes in porcine Escherichia coli isolates (2010–2020) and genomic characterization of mcr-2-positive E. coli

et al. 2022

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“…With multidrug resistance continuously increasing, colistin now belongs to the last-resort antibiotics. Plasmid-bound mcr alleles that mediate resistance to the antimicrobial compound are of great concern in particular if plasmid encoded due to the risk of rapid spread ( Smelikova et al, 2021 ). Several mcr genes have been found, with mcr-9 first identified in Salmonella Typhimurium ( Carroll et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China

et al. 2022

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Salmonella enterica is a zoonotic food-borne pathogen threatening public health around the world. As is the case with many other pathogens, the spread of mobilized colistin resistance (mcr) alleles is of grave concern. In this study, totally 689 clinical Salmonella isolates were collected from a local hospital in Hangzhou, Zhejiang Province, China between 2009 and 2018. Resistance genes were screen by PCR. Two mcr-9-positive Salmonella strains S15 and S639 were identified which belong to serotype Typhimurium and Thompson, respectively. We observed that both mcr-9 genes were located on conjugative IncHI2 plasmids which encoded numerous resistance genes, likely facilitating the dissemination of mcr-9 by co-resistance mechanisms. The mcr-9 cassettes encoded on the two plasmids were not identical: downstream of the mcr-9 genes, we found IS1 on one plasmid (pS15), while the other had a WbuC-IS26 (pS639). Despite the presence of mcr-9 cassettes, the strains were not rendered colistin resistant. Yet, it is of epidemiological importance to implement surveillance to be able to observe and possibly control the spread of mcr-9 due to its potential to mediate resistance to the last-resort antibiotic colistin.

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“…Although ten mobilized colistin resistance genes referred to as mcr-1 to mcr-10 had been identified 16 , mcr-1 is the most predominant type and conferred relatively high level of colistin resistance among MCR family members (MIC=4 or 8μg/ml) 17 . The potential evolution towards even higher level of colistin resistance (HLCR) in mcr-1-positve strains is of great concern.…”

Section: Mainmentioning

confidence: 99%

The fitness landscape of the mobilized colistin resistance gene mcr-1

Guo

Feng

Liang

et al. 2022

Preprint

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The emergence and global discovery of the mobilized colistin resistance gene, mcr-1, limits the clinical effectiveness of colistin as last-resort antibiotic against multiple-drug resistant bacteria. Although MCR-1 exhibits low levels of colistin resistance in E. coli, it is currently unknown whether mcr-1 may potentially evolve a high level of colistin resistance in the future. Here, we generated mcr-1 mutant library that included 27,965 variants, covering 94.44% of the single-nucleotide mutations. We quantified the relative growth of these variant strains under colistin exposure. Notably, most mutations in the catalytic domain, but not in the transmembrane domain, reduce colistin resistance. The structural basis for the mutational effects revealed that the transmembrane domain may contribute to MCR-1 evolution. Altogether, our data shed light on the prediction of MCR-1 evolution, which could be useful for designing novel treatment strategies.

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How to: screening for mcr-mediated resistance to colistin

Cited by 17 publications

References 61 publications

Occurrence of mcr-1 and mcr-2 colistin resistance genes in porcine Escherichia coli isolates (2010–2020) and genomic characterization of mcr-2-positive E. coli

Occurrence of mcr-1 and mcr-2 colistin resistance genes in porcine Escherichia coli isolates (2010–2020) and genomic characterization of mcr-2-positive E. coli

Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China

The fitness landscape of the mobilized colistin resistance gene mcr-1

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