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MCR-3 and MCR-9 confer species-specific increases in colistin MICs
Anna Schumann1, Martin Wiedmann1
1Department of Food Science, Cornell University, Ithaca, NY, USA.
Abstract:
For the clinical treatment of infections with Enterobacteriaceae, the development of resistance to last-resort antimicrobials like colistin is of concern, as it limits treatment options. Since 2015, ten families of mobile colistin resistance (mcr) genes have been discovered; however, our understanding of MCR remains limited because (i) mcr-1 is the most studied variant, (ii) mcr variants are rarely compared and (iii) mcr variants are primarily studied in Escherichia coli, even though studies have shown that mcr variants can confer significantly different phenotypes and that lipid A (i.e. the target of colistin and mcr-modification) structurally differs between bacterial species. To fill this gap, we examined how mcr-3 and mcr-9, as two less frequently studied mcr variants, impact the colistin resistance of laboratory-adapted and real-world (i.e. clinical or food) isolates of E. coli, Salmonella enterica and Klebsiella pneumoniae. We found that while mcr-3 consistently conferred colistin resistance to all tested strains, mcr-9 only conferred resistance to two strains. The fold-change in colistin minimum inhibitory concentrations was significantly impacted by both the bacterial species and the mcr variant but not by whether a strain was a laboratory-adapted or real-world isolate. Overall, our results suggest that while laboratory-adapted strains may provide a good estimate of mcr-mediated colistin resistance of real-world isolates, findings of mcr-mediated phenotypes in one bacterial species should not be extrapolated to another.
Insights
Mobile colistin resistance (mcr) genes like mcr-3 and mcr-9 impact bacterial resistance differently. Understanding these mcr variants across species is crucial for effective antimicrobial treatments.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- The emergence of mobile colistin resistance (mcr) genes poses a significant threat to treating Enterobacteriaceae infections, as colistin is a last-resort antibiotic.
- Limited research comparing different mcr variants and their impact across various bacterial species hinders a full understanding of resistance mechanisms.
Purpose of the Study:
- To investigate the colistin resistance conferred by two less-studied mcr variants, mcr-3 and mcr-9.
- To compare the impact of mcr-3 and mcr-9 on colistin resistance in laboratory-adapted and real-world isolates of E. coli, Salmonella enterica, and Klebsiella pneumoniae.
Main Methods:
- Tested the effect of mcr-3 and mcr-9 on colistin resistance in E. coli, S. enterica, and K. pneumoniae.
- Included both laboratory-adapted and real-world clinical or food isolates.
- Quantified resistance by measuring changes in colistin minimum inhibitory concentrations.
Main Results:
- mcr-3 consistently conferred colistin resistance across all tested bacterial species and isolate types.
- mcr-9 conferred colistin resistance in only two of the tested strains.
- Bacterial species and the specific mcr variant significantly influenced the fold-change in colistin resistance, while isolate type (lab-adapted vs. real-world) did not.
Conclusions:
- The impact of mcr variants on colistin resistance is species-specific and variant-dependent.
- Phenotypic findings from laboratory strains can approximate real-world isolate resistance, but caution is advised when extrapolating results between different bacterial species.
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