Séminaire CIRI (17.06.2025): Dr. Julien VAUBOURGEIX

Julien VAUBOURGEIX, (U1220, INSERM, Toulouse); “ Multiform AMR in bacteria ”

Abstract: Antibiotic recalcitrance refers to a slower rate of death for either a bacterial population or a subpopulation of cells upon antibiotic exposure. It complicates treatment of many bacterial infections by contributing to treatment length, treatment failure, disease recurrence, and the emergence of antimicrobial resistance (AMR). Thus, blocking antibiotic recalcitrance could be a powerful strategy for improving treatment outcomes and reducing AMR rates. Using a forward genetic method for the isolation of antibiotic-recalcitrant mutants, we isolated Mycobacterium smegmatis strains with mutations in the arginine biosynthesis pathway and a tRNA-modifying enzyme adenine-N(1)-methyltransferase. All mutants are recalcitrant or resistant to proteostasis-perturbing antibiotics. We linked these phenotypes to upregulation of the transcriptional regulator WhiB7, highlighting its role as a point of convergence in the regulation of multiple mechanisms of antibiotic recalcitrance and resistance.