PhD defense - Etornam Kofi Kumeko (eq. Bouloc - Genome Biology dpt)

Title: Role of regulatory sRNAs in the adaptation of Staphylococcus aureus to oxidative stress, metal starvation and antibiotic pressure.

Abstract:
Staphylococcus aureus is a highly adaptable pathogen that can survive diverse host-imposed stresses, including nutrient limitation, oxidative stress, and antibiotic exposure. This thesis investigates how small regulatory RNAs (sRNAs) coordinate these adaptive responses at the post-transcriptional level. Under iron limitation, ribosome profiling revealed that the sRNA IsrR represses translation of gabT, a gene involved in central metabolism, highlighting its role in metabolic reprogramming. Consistently, IsrR also downregulates the non-essential iron–sulfur enzyme MiaB by directly inhibiting translation, contributing to an iron-sparing response. In oxidative stress conditions, deletion of rsaE confers increased resistance to reactive oxygen species, identifying RsaE as a negative regulator of stress adaptation acting through pathways involving Mn-superoxide dismutase, CcpA, and SigB. In the context of antibiotic exposure, the sRNA RsaA modulates susceptibility to fluoroquinolones and β-lactams by controlling the global regulator MgrA and associated efflux systems, linking sRNA regulation to antibiotic resistance. Together, these findings establish sRNAs as key integrators of metabolism, stress responses, and antibiotic adaptation in S. aureus, providing new insights into bacterial physiology and potential antimicrobial targets.

Jury members:
Olga SOUTOURINA: Professor, Institut de Biologie Intégrative de la Cellule Université Paris-Saclay, Examiner
Yoann AUGAGNEUR: Professor, Bacterial Regulatory RNAs & Medicine Université de Rennes 1 – Faculty of Pharmacy, Reviewer and Examiner
Pierre MANDIN: Chargé de Recherche, HDR, Laboratoire de Chimie Bactérienne Université Aix Marseille, Reviewer and Examiner
Aurélia HIRON: Asst. Professor, HDR, Infectiologie et Santé Publique Université de Tours, Examiner