Genomic Characterization of ESBL- and Carbapenemase-Positive Enterobacteriaceae Co-harboring mcr-9 in Japan
| Autor: | Masaru Komatsu, Tomokazu Kuchibiro, Akihiro Nakamura, Isao Nishi, Makoto Niki, Tatsuya Nakamura |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
mcr-9 Klebsiella pneumoniae Biology whole-genome sequence medicine.disease_cause Microbiology Antibiotic resistance Plasmid Multiplex polymerase chain reaction polycyclic compounds medicine colistin antimicrobial resistance Escherichia coli Original Research Southern blot biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Enterobacteriaceae QR1-502 Colistin bacteria multidrug-resistant Enterobacteriaceae hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Frontiers in Microbiology, Vol 12 (2021) Frontiers in Microbiology |
| ISSN: | 1664-302X |
| Popis: | Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of mcr-1 to mcr-9 of ESBL-producing Escherichia coli (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring mcr genes (especially mcr-9). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities. Colistin susceptibility testing and multiplex PCR targeting mcr-1 to mcr-9 were performed for all strains with S1-nuclease pulsed-field gel electrophoresis, Southern blot hybridization, and whole-genome sequencing (WGS) with hybrid assembly performed for mcr gene-carrying strains. Two CPE strains showed a MIC ≥ 4 μg/ml in colistin susceptibility testing, with no known resistance mechanism detected. However, PCR conducted on all target strains detected three mcr-9-carrying strains showing colistin susceptibility. The blaCTX–M–62-positive E. coli THUN648 strain simultaneously carried blaCTX–M–62 and mcr-9 on a 275-kbp plasmid. Besides, blaIMP–6 + blaCTX–M–2-positive Klebsiella pneumoniae THUN262 and blaGES–24-positive Enterobacter kobei THUN627 had mcr-9 encoded on the chromosome. Only THUN627 encoded qseB/C, which is suggested to be a regulatory gene for mcr-9, downstream of mcr-9. However, this strain showed no increased expression of these genes in mRNA quantitative analysis under colistin exposure. Colistin MICs of ESBL-Ec and CPE in Japan were all below 2 μg/ml, which is below the epidemiological cutoff (ECOFF) value (https://eucast.org/) or clinical breakpoint (CB) (CLSI M100-S30) reported for colistin, indicating neither “microbiological” nor “clinical” resistance. Several colistin-susceptible Enterobacteriaceae carrying silent mcr-9 encoded on plasmids and chromosomes have already spread worldwide along with other antimicrobial resistance genes. However, the mechanism of colistin resistance by mcr-9 remains unclear. |
| Databáze: | OpenAIRE |
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