Epitranscriptomic response to antibiotics in Vibrio cholerae
Antimicrobial resistance develops as a major problem in infectious diseases treatment. Starting with a high-density Transposon insertion library in Vibrio cholerae and following its evolution by TN-seq in the presence of antibiotics, we have linked 23 tRNA and rRNA modification enzymes with specific responses to various antibiotics. In particular, deletion of tRNA guanine transglycosylase tgt leads to strong aminoglycoside sensitivity. Tgt is responsible for the queuosine (Q) modification of tRNA-tyrosine at the anti-codon loop wobble position. We used molecular reporters for translation fidelity and efficiency as well as a proteomics analysis to further characterize molecular mechanisms behind the aminoglycoside sensitive phenotype in the absence of tgt/Q modification.
We show that (i) the absence of Q impacts tyrosine codon decoding and leads to translational reprogramming in response to stress. (ii) A protein’s codon usage bias can influence its translation in a Q modification dependent way. (iii) Candidate transcripts subject to such post-transcriptional regulation can be identified based on their codon content in bacteria. Our results highlight the existence of an epitranscriptomic and translational control of the bacterial response to antibiotic stress.
Short bio
I did my PhD on the mechanisms of restart of arrested replication forks in E. coli at the CNRS at Paris with Bénédicte Michel (2008), and I did a postdoc at Institut Pasteur on stress responses linked with horizontal gene transfer in Vibrio cholerae in Didier Mazel’s team. Now my group at Institut Pasteur & IBPC, Paris, focuses on how bacteria deal with antibiotic stress, and particularly on the role of RNA modifications on bacterial adaptation.
Laboratoire
Institut Pasteur – Unité « Plasticité du Génome Bactérien », Département Génomes et Génétique
Invitée par
research axis, Pascale Serror & Francis Repoila
