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Journal articles
β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity
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.
Cited literature [56 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01691736
Contributor : Isabelle Hoffmann Connect in order to contact the contributor
Submitted on : Wednesday, January 24, 2018 - 12:21:04 PM
Last modification on : Monday, November 22, 2021 - 4:14:05 PM
Long-term archiving on: : Thursday, May 24, 2018 - 6:35:10 PM
Contributor : Isabelle Hoffmann Connect in order to contact the contributor
Submitted on : Wednesday, January 24, 2018 - 12:21:04 PM
Last modification on : Monday, November 22, 2021 - 4:14:05 PM
Long-term archiving on: : Thursday, May 24, 2018 - 6:35:10 PM
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Nat Commun_2607.pdf
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