A qnr-plasmid allows aminoglycosides to induce SOS in Escherichia coli

Anamaria Babosan1, David Skurnik2, Anaëlle Muggeo3

  • 1Inserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, Reims, France.

Elife
|January 17, 2022
PubMed

Insights

Aminoglycosides can trigger the SOS response in E. coli, leading to increased plasmid-mediated quinolone resistance (PMQR) gene expression. This occurs through nitric oxide (NO) accumulation, driven by plasmid genes ORF3 and ORF4.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Plasmid-mediated quinolone resistance (PMQR) genes confer bacterial resistance to fluoroquinolones, risking treatment failure.
  • Sub-inhibitory concentrations of fluoroquinolones induce the SOS response in Escherichia coli, regulating PMQR gene expression via LexA.
  • The expression of some PMQR qnr genes is controlled by the SOS master regulator, LexA.

Purpose of the Study:

  • To investigate the effect of aminoglycosides on the SOS response and qnrD gene expression in E. coli.
  • To elucidate the mechanism by which aminoglycosides induce the SOS response and NO accumulation.
  • To identify the plasmid-encoded genes responsible for NO synthesis and detoxification pathway regulation.

Main Methods:

  • Characterization of a qnrD-carrying plasmid in E. coli.
  • Assessing the induction of the SOS response by aminoglycosides.
  • Measuring nitric oxide (NO) accumulation.
  • Identifying and characterizing plasmid genes ORF3 and ORF4.
  • Investigating the roles of ORF3 and ORF4 in NO synthesis and detoxification.

Main Results:

  • Aminoglycosides induce the SOS response in E. coli, leading to elevated qnrD transcription.
  • SOS induction is caused by nitric oxide (NO) accumulation in the presence of sub-MIC aminoglycosides.
  • Plasmid genes ORF3 and ORF4 drive NO accumulation: ORF3 encodes an NO-synthesizing oxidoreductase, and ORF4 encodes a transcription factor repressing NO detoxification.
  • The Hmp-mediated NO detoxification pathway in E. coli is repressed by ORF4.

Conclusions:

  • Aminoglycosides can induce the SOS response in E. coli, contributing to the spread of plasmid-mediated quinolone resistance.
  • Plasmid-borne genes ORF3 and ORF4 play a critical role in NO synthesis and the repression of NO detoxification, mediating aminoglycoside-induced SOS response.
  • These findings highlight that antibiotic classes beyond fluoroquinolones can trigger the SOS response, with significant implications for antibiotic stewardship and resistance prevention strategies.