Séminaire CIRI (23.10.2024): Pr. Paul TURNER

Pr. Paul TURNER, Yale school of medecine; “ Developing phage therapy against antimicrobial resistant bacterial infections ”.

Abstract: The rise of antibiotic resistance warrants exploration of novel approaches for addressing difficult to treat bacterial infections. Phage therapy is an older technology that precedes discovery and widespread use of chemical antibiotics, instead harnessing bacteria-specific viruses (bacteriophages) to target and kill infecting bacteria. However, a limitation of phage therapy is the ability for target bacteria to evolve resistance to these administered viruses. One promising approach is to use phages that steer bacteria to evolve phage resistance that coincides with reduced bacterial pathogenicity. In particular, naturally-occurring phages can be used because they kill the target bacteria, while predictably selecting for evolution of costly phage resistance (evolutionary trade-offs): reduced virulence and/or increased antibiotic sensitivity. By utilizing virulence factors as receptor binding sites, the phages exert selection for bacteria to evolve phage resistance by modifying (or losing) the virulence factor, potentially reducing bacterial pathogenicity. Examples include phages that utilize bacterial lipopolysaccharides, efflux-pump proteins, and pili as binding sites, to kill target bacteria while selecting for phage resistance that coincides with useful clinical traits such as antibiotic re-sensitization and reduced tissue inflammation. These in vitro observations are compared to phenotypic, genetic and metagenomics analyses of microbes isolated longitudinally from patient samples before, during and after emergency phage therapy treatments. Throughout, the talk emphasizes how ‘evolutionary medicine’ approaches are critical for developing modern phage therapy, and how collaborations among basic scientists, clinicians and physicians are crucial for safely developing biotechnologies that address the antibiotic resistance crisis.

hôte: Anne Chevallereau