Skip to Main content Skip to Navigation
Journal articles

Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin

Abstract : High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin-antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin.
Document type :
Journal articles
Complete list of metadatas

Cited literature [65 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01385427
Contributor : Anne Lassailly-Bondaz <>
Submitted on : Friday, October 21, 2016 - 12:58:13 PM
Last modification on : Friday, April 3, 2020 - 12:32:02 PM

File

journal.pgen.1003144.PDF
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Steve P. Bernier, David Lebeaux, Alicia S. Defrancesco, Amandine Valomon, Guillaume Soubigou, et al.. Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin. PLoS Genetics, Public Library of Science, 2013, 9 (1), pp.e1003144. ⟨10.1371/journal.pgen.1003144⟩. ⟨pasteur-01385427⟩

Share

Metrics

Record views

544

Files downloads

482