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Genomic Characterization of VIM and MCR Co-Producers: The First Two Clinical Cases, in Italy
Vittoria Mattioni Marchetti1,2, Ibrahim Bitar1,2, Mario Sarti3
1Department of Microbiology, Faculty of Medicine and University Hospital in Pilsen, Charles University, 306 05 Pilsen, Czech Republic.
Background:
the co-production of carbapenemases and mcr-genes represents a worrisome event in the treatment of Enterobacteriaceae infections. The aim of the study was to characterize the genomic features of two clinical Enterobacter cloacae complex (ECC) isolates, co-producing VIM and MCR enzymes, in Italy.
Methods:
species identification and antibiotic susceptibility profiling were performed using MALDI-TOF and broth microdilution methods, respectively. Transferability of the bla VIM- and mcr- type genes was verified through conjugation experiment. Extracted DNA was sequenced using long reads sequencing technology on the Sequel I platform (PacBio).
Results:
the first isolate showed clinical resistance against ertapenem yet was colistin susceptible (EUCAST 2020 breakpoints). The mcr-9.2 gene was harbored on a conjugative IncHI2 plasmid, while the bla VIM-1 determinant was harbored on a conjugative IncN plasmid. The second isolate, resistant to both carbapenems and colistin, harbored: mcr-9 gene and its two component regulatory genes for increased expression on the chromosome, mcr-4.3 on non-conjugative (yet co-transferable) ColE plasmid, and bla VIM-1 on a non-conjugative IncA plasmid.
Conclusions:
to our knowledge, this is the first report of co-production of VIM and MCR in ECC isolates in Italy.
Insights
Two Italian Enterobacter cloacae complex isolates co-produced VIM carbapenemases and MCR-type genes, raising concerns for treating Enterobacteriaceae infections. This study details their genomic features and resistance mechanisms.
Area of Science:
- Medical Microbiology
- Genomics
- Antimicrobial Resistance
Background:
- Co-production of carbapenemases and MCR-type genes is a significant threat in treating Enterobacteriaceae infections.
- Enterobacter cloacae complex (ECC) isolates are increasingly recognized for harboring antimicrobial resistance genes.
Purpose of the Study:
- To characterize the genomic features of two Italian clinical ECC isolates co-producing VIM and MCR enzymes.
- To investigate the genetic basis of resistance to carbapenems and colistin in these isolates.
Main Methods:
- Species identification and antibiotic susceptibility profiling using MALDI-TOF and broth microdilution.
- Verification of gene transferability via conjugation experiments.
- Whole-genome sequencing using long-read PacBio Sequel I technology.
Main Results:
- One isolate harbored mcr-9.2 on an IncHI2 plasmid and blaVIM-1 on an IncN plasmid, showing ertapenem resistance but colistin susceptibility.
- The second isolate exhibited resistance to both carbapenems and colistin, with mcr-9 on the chromosome and mcr-4.3 on a ColE plasmid, alongside blaVIM-1 on an IncA plasmid.
- Both isolates demonstrated complex plasmid-mediated and chromosomal resistance mechanisms.
Conclusions:
- This is the first report of VIM and MCR co-production in Enterobacter cloacae complex isolates in Italy.
- The findings highlight the emergence of multidrug-resistant ECC strains with significant public health implications.
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