A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>

Bacteria within biofilms may be exposed to sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. Cell-to-cell contact within biofilms facilitates horizontal gene transfers and favors induction of the SOS response. Altogether, it participates in the emergence of antibiotic resistance. Amin...

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Main Authors: Anamaria Babosan, Margaux Gaschet, Anaëlle Muggeo, Thomas Jové, David Skurnik, Marie-Cécile Ploy, Christophe de Champs, Fany Reffuveille, Thomas Guillard
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/11/6/715
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author Anamaria Babosan
Margaux Gaschet
Anaëlle Muggeo
Thomas Jové
David Skurnik
Marie-Cécile Ploy
Christophe de Champs
Fany Reffuveille
Thomas Guillard
author_facet Anamaria Babosan
Margaux Gaschet
Anaëlle Muggeo
Thomas Jové
David Skurnik
Marie-Cécile Ploy
Christophe de Champs
Fany Reffuveille
Thomas Guillard
author_sort Anamaria Babosan
collection DOAJ
description Bacteria within biofilms may be exposed to sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. Cell-to-cell contact within biofilms facilitates horizontal gene transfers and favors induction of the SOS response. Altogether, it participates in the emergence of antibiotic resistance. Aminoglycosides at sub-MICs can induce the SOS response through NO accumulation in <i>E. coli</i> carrying the small plasmid with the quinolone resistance <i>qnrD</i> gene (pDIJ09-518a). In this study, we show that in <i>E. coli</i> pDIJ09-518a, the SOS response triggered by sub-MICs of aminoglycosides has important consequences, promoting genetic rearrangement in class 1 integrons and biofilm formation. We found that the integrase expression was increased in <i>E. coli</i> carrying pDIJ09-518a in the presence of tobramycin, which was not observed for the WT isogenic strain that did not carry the <i>qnrD</i>-plasmid. Moreover, we showed that biofilm production was significantly increased in <i>E. coli</i> WT/pDIJ09-518a compared to the WT strain. However, such a higher production was decreased when the Hmp-NO detoxification pathway was fully functional by overexpressing Hmp. Our results showing that a <i>qnrD</i>-plasmid can promote biofilm formation in <i>E. coli</i> and potentiate the acquisition and spread of resistance determinants for other antibiotics complicate the attempts to counteract antibiotic resistance and prevention of biofilm development even further. We anticipate that our findings emphasize the complex challenges that will impact the decisions about antibiotic stewardship, and other decisions related to retaining antibiotics as effective drugs and the development of new drugs.
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spelling doaj.art-13959c0bacca439bb17a41892e031c802023-11-23T15:16:03ZengMDPI AGAntibiotics2079-63822022-05-0111671510.3390/antibiotics11060715A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>Anamaria Babosan0Margaux Gaschet1Anaëlle Muggeo2Thomas Jové3David Skurnik4Marie-Cécile Ploy5Christophe de Champs6Fany Reffuveille7Thomas Guillard8Inserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, 51100 Reims, FranceUniversité de Limoges, Inserm, CHU Limoges, UMR-S 1092, 87032 Limoges, FranceInserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, 51100 Reims, FranceUniversité de Limoges, Inserm, CHU Limoges, UMR-S 1092, 87032 Limoges, FranceInstitut Necker-Enfants Malades, Inserm U1151-Equipe 11, Université Paris Descartes, 75015 Paris, FranceUniversité de Limoges, Inserm, CHU Limoges, UMR-S 1092, 87032 Limoges, FranceInserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, 51100 Reims, FranceEA 4691 BiOS, SFR CAP-Santé, Université de Reims Champagne-Ardenne, 51100 Reims, FranceInserm UMR-S 1250 P3Cell, SFR CAP-Santé, Université de Reims-Champagne-Ardenne, 51100 Reims, FranceBacteria within biofilms may be exposed to sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. Cell-to-cell contact within biofilms facilitates horizontal gene transfers and favors induction of the SOS response. Altogether, it participates in the emergence of antibiotic resistance. Aminoglycosides at sub-MICs can induce the SOS response through NO accumulation in <i>E. coli</i> carrying the small plasmid with the quinolone resistance <i>qnrD</i> gene (pDIJ09-518a). In this study, we show that in <i>E. coli</i> pDIJ09-518a, the SOS response triggered by sub-MICs of aminoglycosides has important consequences, promoting genetic rearrangement in class 1 integrons and biofilm formation. We found that the integrase expression was increased in <i>E. coli</i> carrying pDIJ09-518a in the presence of tobramycin, which was not observed for the WT isogenic strain that did not carry the <i>qnrD</i>-plasmid. Moreover, we showed that biofilm production was significantly increased in <i>E. coli</i> WT/pDIJ09-518a compared to the WT strain. However, such a higher production was decreased when the Hmp-NO detoxification pathway was fully functional by overexpressing Hmp. Our results showing that a <i>qnrD</i>-plasmid can promote biofilm formation in <i>E. coli</i> and potentiate the acquisition and spread of resistance determinants for other antibiotics complicate the attempts to counteract antibiotic resistance and prevention of biofilm development even further. We anticipate that our findings emphasize the complex challenges that will impact the decisions about antibiotic stewardship, and other decisions related to retaining antibiotics as effective drugs and the development of new drugs.https://www.mdpi.com/2079-6382/11/6/715biofilm<i>qnr</i><i>Escherichia coli</i>integron
spellingShingle Anamaria Babosan
Margaux Gaschet
Anaëlle Muggeo
Thomas Jové
David Skurnik
Marie-Cécile Ploy
Christophe de Champs
Fany Reffuveille
Thomas Guillard
A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
Antibiotics
biofilm
<i>qnr</i>
<i>Escherichia coli</i>
integron
title A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
title_full A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
title_fullStr A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
title_full_unstemmed A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
title_short A <i>qnrD</i>-Plasmid Promotes Biofilm Formation and Class 1 Integron Gene Cassette Rearrangements in <i>Escherichia coli</i>
title_sort i qnrd i plasmid promotes biofilm formation and class 1 integron gene cassette rearrangements in i escherichia coli i
topic biofilm
<i>qnr</i>
<i>Escherichia coli</i>
integron
url https://www.mdpi.com/2079-6382/11/6/715
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