Project #10921
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#10921 : Analysis of DNA methylation in the presence and absence of antibiotics in wt and mutant V. cholerae
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Name of Applicant : Baharoglu Zeynep
Date of application : 19-01-2018
Unit : Bacterial Genome Plasticity
Location : Paris
Phone : 9483
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Project context and summary :

The goal of this project is to study the strategies undertaken by Gram negative bacteria to respond to sub-lethal antibiotic stress. We previously established that low doses of antibiotics that do not affect bacterial growth still induce stress responses in bacteria and suggest that understanding the mechanisms underlying these stress responses can prime strategies to increase antibiotic treatment efficiency. In this project, we will address consequences of stress responses and pathways activated by sub-MICs of antibiotics at epigenetic levels. Our transcriptomic data led to the identification of a new orphan DNA methylase (not associated with a restriction enzyme), which is highly upregulated in the presence of sub-MIC aminoglycosides. This points to a differential DNA methylation profile upon antibiotics treatment. The methylation status of the cytosines in different conditions will be investigated by NGS (Bisulfite-WGS), in order to detect possible epigenetic changes occurring in response to antibiotic treatment. Methylation may be an epigenetic response to antibiotic stress. The role of adenine methylation in bacteria is well described. In contrast, the role of cytosine methylation remains unknown. Therefore we will characterize the different methylation mutants of cytosines, to establish methylation profiles. A preliminary analysis with encouraging results was performed together with the C3BI in 2017.

Related team publications :
Baharoglu Z, Mazel D. (2011) Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics: a route towards multiresistance. Antimicrob Agents Chemother. 55(5):2438-41.
Baharoglu Z, Krin E & Mazel D (2013) RpoS Plays a Central Role in the SOS Induction by Sub-Lethal Aminoglycoside Concentrations in Vibrio cholerae. Plos Genetics 9. e1003421.
Baharoglu Z, Babosan A & Mazel D (2014) Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase. Nucleic Acids Res 42: 2366-2379.
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Project Type : Medium
Status : Closed
Global Satisfaction for this application : Excellent (5/5)

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