Wébinaire – Marie-Ève Picard, Ph.D., mercredi 28 octobre à 12h15

PROTEO est heureux de lancer une nouvelle série de webinaires mensuels mettant en lumière les projets lauréats du concours Nouvelles initiatives collaboratives 2024. Pour inaugurer cette série, nous avons le plaisir de vous inviter à la présentation de Marie-Ève Picard, Ph. D., stagiaire postdoctorale à l’Université Laval, le mercredi 28 octobre à 12 h 15. La présentation portera sur l’un des projets lauréats, réalisé par Christian Landry, Rong Shi et Sophie Gobeil.

Lien du wébinaire :  https://uqam.zoom.us/j/85302387629

“Epistasis limits but does not prevent the transfer of mutation-drug resistance mapping across 600 million years of fungal evolution”
Whether different pathogens acquire resistance to antimicrobials through the same mutations is a major question in evolution and microbiology. Most antifungal drugs are used to treat infections caused by multiple fungal species, many of which have diverged for millions of years. If the evolution of resistance was to converge onto the same set of mutations across species, knowing the mechanism of resistance in one would allow us to predict and track it in others. The extent of this convergence remains unknown due to the lack of systematic data on resistance mutations. Here, we quantify the conservation of resistance mutations in the cytosine deaminase (CD), a protein responsible for resistance to flucytosine, one of the oldest antifungal drugs. By comparing the crystal structures of this enzyme through 600 My of evolution, we show that the CD structure is highly conserved. We compared the full CD mutational resistance spectrum of resistance from an ascomycete and a basidiomycete. We found that resistance mutations in one ortholog can be used to predict resistance in the other at a high level of accuracy. However, because of epistasis, around 10% of mutations have distinct effects in the two orthologs, which imposes an upper limit to the transferability of the knowledge of resistance mutations from one species to another. Using biochemical assays and by structural characterization of several mutants, we identify distinct mechanisms of epistasis, one important being that the local physiochemical environment of some position has evolved in a way that makes the same substitutions destabilizing or entirely inactivating in an ortholog-specific manner. Our results show that resistance mutations can be conserved in fungi across hundreds of millions of years of evolution but that epistasis eventually limits the accuracy of these predictions.

Programmation des prochains webinaires : 

• 18 novembre : Projet collaboratif de Nicolas Bisson (ULaval) et Steve Jean (UdeS)
• 9 décembre : Projet collaboratif de Denis Leclerc (ULaval) et Steve Bourgault (UQAM)
• 20 janvier : Projet collaboratif de Joshua Cloutier-Beaupré (CNETE) et Sylvain Moineau (ULaval)
• 17 février : Projet collaboratif de Daniela Quaglia (UQAM), Steve Bourgault (UQAM) et Habib Horchani (Cégep de Rivière-du-Loup)
• 17 mars : Projet collaboratif de Denis Giguère et Éric Biron (ULaval)
• 14 avril : Projet collaboratif de Steve Shih et David Kwan (Concordia)

En espérant vous y voir en grand nombre !