Abstract : Regardless of their targets and modes of action, subinhibitory concentrations of antibiotics can have an impact on cell physiology and trigger a large variety of cellular responses in different bacterial species. Subinhibitory concentrations of β-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of β-lactam antibiotics induce the RpoS regulon. RpoS regulon induction is required for PolIV-dependent mutagenesis because it diminishes the control of DNA-replication fidelity by depleting MutS in E. coli, Vibrio cholerae and Pseudomonas aeruginosa. We also show that in E. coli, the reduction in mismatch-repair activity is mediated by SdsR, the RpoS-controlled small RNA. In summary, we show that mutagenesis induced by subinhibitory concentrations of antibiotics is a genetically controlled process. Because this mutagenesis can generate mutations conferring antibiotic resistance, it should be taken into consideration for the development of more efficient antimicrobial therapeutic strategies.
https://hal-pasteur.archives-ouvertes.fr/pasteur-01691736 Contributor : Isabelle HOFFMANNConnect in order to contact the contributor Submitted on : Wednesday, January 24, 2018 - 12:21:04 PM Last modification on : Thursday, April 7, 2022 - 10:10:34 AM Long-term archiving on: : Thursday, May 24, 2018 - 6:35:10 PM
A. Gutierrez, L. Laureti, S. Crussard, H. Abida, A. Rodríguez-Rojas, et al.. β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity. Nature Communications, Nature Publishing Group, 2013, 4, pp.1610. ⟨10.1038/ncomms2607⟩. ⟨pasteur-01691736⟩