A qnr-plasmid allows aminoglycosides to induce SOS in Escherichia coli
- Inserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, France
- Inserm U1151-Equipe 11, Université Paris Descartes, France
- Brigham and Women's Hospital, United States
- Institut Pasteur, France
- Université de Limoges, Inserm, France
- PSL Research University, CNRS, France
- Centre Hospitalier de Troyes, France
Abstract
The plasmid-mediated quinolone resistance (PMQR) genes have been shown to promote high-level bacterial resistance to fluoroquinolone antibiotics, potentially leading to clinical treatment failures. In Escherichia coli, sub-minimum inhibitory concentrations (sub-MICs) of the widely used fluoroquinolones are known to induce the SOS response. Interestingly, the expression of several PMQR qnr genes is controlled by the SOS master regulator, LexA. During the characterization of a small qnrD-plasmid carried in E. coli, we observed that the aminoglycosides become able to induce the SOS response in this species, thus leading to the elevated transcription of qnrD. Our findings show that induction of the SOS response is due to nitric oxide (NO) accumulation in presence of sub-MIC of aminoglycosides. We demonstrated that the NO accumulation is driven by two plasmid genes, ORF3 and ORF4, whose products act at two levels. ORF3 encodes a putative flavin adenine dinucleotide (FAD)-binding oxidoreductase which helps NO synthesis, while ORF4 codes for a putative fumarate and nitrate reductase (FNR)-type transcription factor, related to an O2-responsive regulator of hmp expression, able to repress the Hmp-mediated NO detoxification pathway of E. coli. Thus, this discovery, that other major classes of antibiotics may induce the SOS response could have worthwhile implications for antibiotic stewardship efforts in preventing the emergence of resistance.
Data availability
Source data are provided as a Source Data file. Flow cytometry data have been deposited in FlowRepository as FR-FCM-Z3MR repository ID (http://flowrepository.org/id/RvFrzhOtiB4Hrd9yMMTEF2gAckZvYVa365phD9U0fVTabQb7ibCDqV8Gzbgb02dm).
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Author details
Funding
Université de Reims Champagne-Ardenne
- Anamaria Babosan
- Christophe de Champs
- Thomas Guillard
Conseil Regional de Champagne-Ardenne
- Anamaria Babosan
- Christophe de Champs
- Thomas Guillard
Association pour le Developpement de la Microbiologie et de l'Immunologie Rémoises
- Anamaria Babosan
International Union of Biochemistry and Molecular Biology
- Anamaria Babosan
Agence Nationale de la Recherche (ANR-10-LABX-62- IBEID)
- Didier Mazel
Centre National de la Recherche Scientifique
- Zeynep Baharoglu
- Didier Mazel
Institut Pasteur
- Zeynep Baharoglu
- Didier Mazel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Babosan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A qnr-plasmid allows aminoglycosides to induce SOS in Escherichia coli
eLife 11:e69511.
https://doi.org/10.7554/eLife.69511
