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Loss of mcr Genes Mediated by Plasmid Elimination and ISApl1

Pei Zhang1,2, Li Bai2, Yan Li3

  • 1Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Antimicrobial Agents and Chemotherapy
|June 19, 2019
PubMed

Insights

The plasmid carrying mcr-1 and mcr-3.19 genes can be eliminated without colistin, but genetic elements drive the loss of these antimicrobial resistance genes during passages.

Area of Science:

  • Molecular Biology
  • Antimicrobial Resistance Research
  • Genetics

Background:

  • The plasmid pCP53-mcr1_3 harbors genes conferring resistance to colistin, a critical antibiotic.
  • Understanding the stability and potential elimination of such plasmids is crucial for combating antimicrobial resistance.

Purpose of the Study:

  • To investigate the stability of the pCP53-mcr1_3 plasmid encoding mcr-1 and mcr-3.19 under different conditions.
  • To determine the mechanisms of mcr gene loss and plasmid elimination during bacterial culture.

Main Methods:

  • Plasmid stability was assessed through serial cultural passages with and without colistin exposure.
  • S1-pulsed-field gel electrophoresis (PFGE) and nanopore MinION sequencing were employed for genetic characterization.

Main Results:

  • Both mcr-1 and mcr-3.19 genes were lost in specific subclones, indicating plasmid instability.
  • Genetic excision events, including ISApl1-mcr-1-pap2, and large multidrug resistance (MDR) region deletions mediated by ISApl1 were identified.
  • Plasmid elimination occurred, particularly in the absence of colistin pressure.

Conclusions:

  • The eradication of mcr genes from the pCP53-mcr1_3 plasmid is feasible without colistin exposure.
  • Genetic mechanisms like ISApl1-mediated excision and deletion play a significant role in the loss of antimicrobial resistance genes.
  • Further research is needed to fully elucidate the factors governing these elimination processes.
Keywords:
mcr genesnanopore sequencingplasmids

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