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Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.

By Z. Baharoglu, A. Babosan and D. Mazel

Abstract

International audienceSub-inhibitory concentrations (sub-MIC) of antibiotics play a very important role in selection and development of resistances. Unlike Escherichia coli, Vibrio cholerae induces its SOS response in presence of sub-MIC aminoglycosides. A role for oxidized guanine residues was observed, but the mechanisms of this induction remained unclear. To select for V. cholerae mutants that do not induce low aminoglycoside-mediated SOS induction, we developed a genetic screen that renders induction of SOS lethal. We identified genes involved in this pathway using two strategies, inactivation by transposition and gene overexpression. Interestingly, we obtained mutants inactivated for the expression of proteins known to destabilize the RNA polymerase complex. Reconstruction of the corresponding mutants confirmed their specific involvement in induction of SOS by low aminoglycoside concentrations. We propose that DNA lesions formed on aminoglycoside treatment are repaired through the formation of single-stranded DNA intermediates, inducing SOS. Inactivation of functions that dislodge RNA polymerase leads to prolonged stalling on these lesions, which hampers SOS induction and repair and reduces viability under antibiotic stress. The importance of these mechanisms is illustrated by a reduction of aminoglycoside sub-MIC. Our results point to a central role for transcription blocking at DNA lesions in SOS induction, so far underestimated

Topics: MESH: Anti-Bacterial Agents/pharmacology*, MESH: Bacterial Proteins/genetics, MESH: Transcription Factors/metabolism, MESH: Transcription Factors/physiology*, MESH: Bacterial Proteins/metabolism, MESH: Transcription, Genetic*, MESH: Ultraviolet Rays, MESH: Vibrio cholerae/drug effects, MESH: Vibrio cholerae/enzymology, MESH: Vibrio cholerae/genetics*, MESH: Bacterial Proteins/physiology*, MESH: DNA Damage, MESH: Gene Deletion, MESH: DNA Helicases/genetics, MESH: DNA Helicases/metabolism, MESH: DNA Helicases/physiology*, MESH: DNA-Directed RNA Polymerases/metabolism, MESH: Escherichia coli/radiation effects, MESH: Genes, Bacterial, MESH: MutS DNA Mismatch-Binding Protein/genetics, MESH: Mutation, MESH: Ribonuclease H/metabolism, MESH: SOS Response (Genetics)*, MESH: Tobramycin/pharmacology, MESH: Transcription Factors/genetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.GEN]Life Sciences [q-bio]/Genetics
Publisher: 'Oxford University Press (OUP)'
Year: 2014
DOI identifier: 10.1093/nar/gkt1259
OAI identifier: oai:HAL:pasteur-01423602v1
Provided by: HAL-Pasteur
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