β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity

A. Gutierrez (1) , L. Laureti (1) , S. Crussard (1) , H. Abida (1) , A. Rodríguez-Rojas (2) , J. Blázquez (2) , Z. Baharoglu (3) , D. Mazel (3) , F. Darfeuille (4) , J. Vogel (5) , I. Matic (1)

1 U1001 - Robustesse et évolvabilité de la vie
2 Departamento de Biotecnología Microbiana
3 PGB - Plasticité du Génome Bactérien - Bacterial Genome Plasticity
4 ARNA - Régulations Naturelles et Artificielles
5 JMU - Julius-Maximilians-Universität Würzburg

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.

Domains: Life Sciences [q-bio]

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, 2013, 4, pp.1610. ⟨10.1038/ncomms2607⟩. ⟨pasteur-01691736⟩