Clostridium Triple Shot SEMINARS

Title
RNomics during C. difficile infection cycle: from identification to function

Speaker
Olga Soutourina, Professor  at the Paris-Saclay University

Abstract
Clostridioides difficile is the leading cause of healthcare associated diarrhoea in industrialized countries. Many aspects of C. difficile pathogenesis associated with adaptation strategies remain poorly understood. Non-coding RNAs (ncRNAs) shape virulence in many pathogens and modulate host responses, however, their role in C. difficile infection has not been explored. Clostridia have developed unique RNA-based mechanisms and associated machineries (e.g. RNA chaperone protein Hfq), which differ from both Gram-positive Bacillota like bacilli and staphylococci, and well-studied Gram-negative enterobacteria. Studying this ancient group of bacteria should reveal other strategies of adaptation and insights into the evolutionary history of bacterial riboregulation. Using bioinformatics and genome-wide approaches we identified more than 200 ncRNAs in C. difficile, the majority being specific to this pathogen. Our recent dual RNA-seq data show that many of ncRNAs are expressed during infection, indicating that they contribute to shape virulence and adaptation of C. difficile to its host. Some of these ncRNAs participate in the regulation of sporulation process in accordance with accumulating evidence for the importance of RNA-based mechanisms in the control of this key step in C. difficile infection cycle including Hfq and Hfq-binding ncRNAs. To control genetic exchanges during the infection cycle, C. difficile survives in phage-rich gut communities by relying on defense systems like CRISPR-Cas, Toxin-Antitoxin (TA) and abortive infection (Abi) contributing to prophage maintenance, prevention of phage infection, and stress response. RNAs have emerged as key components of these systems including CRISPR RNAs and antitoxin RNAs within type I and type III TA. We characterized these RNA-based systems in C. difficile that are frequently associated with prophages providing efficient defense against other invading phages or contributing to these regions stability. Overall, these data are shedding new light on the riboregulation mechanisms in C. difficile opening new avenues for specific therapeutic and diagnostic strategies.

Organizers
Mónica Serrano and Adriano O. Henriques

SCANs are weekly seminars that happen every Wednesday at noon by in-house researchers and invited speakers at ITQB NOVA.