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

Z. Baharoglu 1, * A. Babosan 1 D. Mazel 1, *
* Auteur correspondant
Abstract : Sub-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.
Type de document :
Article dans une revue
Nucleic Acids Research, Oxford University Press, 2014, 42 (4), pp.2366-2379. 〈10.1093/nar/gkt1259〉
Liste complète des métadonnées

https://hal-pasteur.archives-ouvertes.fr/pasteur-01423602
Contributeur : Isabelle Hoffmann <>
Soumis le : vendredi 30 décembre 2016 - 14:42:47
Dernière modification le : jeudi 11 janvier 2018 - 06:27:22
Document(s) archivé(s) le : mardi 21 mars 2017 - 01:33:26

Fichier

gkt1259.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Z. Baharoglu, A. Babosan, D. Mazel. Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.. Nucleic Acids Research, Oxford University Press, 2014, 42 (4), pp.2366-2379. 〈10.1093/nar/gkt1259〉. 〈pasteur-01423602〉

Partager

Métriques

Consultations de la notice

185

Téléchargements de fichiers

118