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).
Article and author information
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.
Metrics
-
- 997
- views
-
- 152
- downloads
-
- 5
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A qnr-plasmid allows aminoglycosides to induce SOS in Escherichia coli
eLife 11:e69511.
https://doi.org/10.7554/eLife.69511
Further reading
-
- Microbiology and Infectious Disease
Protein NƐ-lysine acetylation (Kac) modifications play crucial roles in diverse physiological and pathological functions in cells. In prokaryotic cells, there are only two types of lysine deacetylases (KDACs) that are Zn2+- or NAD+-dependent. In this study, we reported a protein, AhCobQ, in Aeromonas hydrophila ATCC 7966 that presents NAD+- and Zn2+-independent KDAC activity. Furthermore, its KDAC activity is located in an unidentified domain (from 195 to 245 aa). Interestingly, AhCobQ has no homology with current known KDACs, and no homologous protein was found in eukaryotic cells. A protein substrate analysis showed that AhCobQ has specific protein substrates in common with other known KDACs, indicating that these KDACs can dynamically co-regulate the states of Kac proteins. Microbiological methods employed in this study affirmed AhCobQ’s positive regulation of isocitrate dehydrogenase (ICD) enzymatic activity at the K388 site, implicating AhCobQ in the modulation of bacterial enzymatic activities. In summary, our findings present compelling evidence that AhCobQ represents a distinctive type of KDAC with significant roles in bacterial biological functions.
-
- Microbiology and Infectious Disease
Influenza A virus transcribes viral mRNAs from the eight segmented viral genome when it infects. The kinetics of viral transcription, nuclear export of viral transcripts, and their potential variation between the eight segments are poorly characterised. Here, we introduce a statistical framework for estimating the nuclear export rate of each segment from a snapshot of in situ mRNA localisation. This exploits the cell-to-cell variation at a single time point observed by an imaging-based in situ transcriptome assay. Using our model, we revealed the variation in the mRNA nuclear export rate of the eight viral segments. Notably, the two influenza viral antigens hemagglutinin and neuraminidase were the slowest segments in the nuclear export, suggesting the possibility that influenza A virus uses the nuclear retention of viral transcripts to delay the expression of antigenic molecules. Our framework presented in this study can be widely used for investigating the nuclear retention of nascent transcripts produced in a transcription burst.
