Speaker: Prof. Patrick Van Dijck
Group Leader - Molecular Biotechnology of Plants and Micro-organisms, Department of Biology, KU Leuven, Leuven, Belgium
Presentation
Host: Dr. Toni Gabaldón, Group Leader - Comparative Genomics - IRB Barcelona
Node: Computational Biology / Cell Pathophysiology
Date: Thursday 2 November 2023, 16.00h
Place: Serratosa Room
IMPORTANT: For attendees outside the PCB community you must register at least 24h before the seminar.
Abstract
The increased prevalence of antifungal drug resistance and emergence of multidrug-resistant species such as Candida auris represent a global public health threat. We have setup high-throughput screenings using different clades of C. auris against a large set of antifungal drugs. Resistant isolates where then evolved for resistance against a second drug. Mapping drug susceptibility responses of such experimentally evolved C. auris strains across diverse antifungals, resulted in combinations that show cross-resistance (XR) but also in combinatios that result in collateral sensitivity (CS). This CS means that a strain that was resistant to drug A and is then evolved for resistance against drug B, then becomes super sensitive towards drug A. Combinations showing CS were then validated using drug cycling and combination therapy, providing a promising direction for future research. We also focused on the Amphothericin B resistance isolates in C. auris and obtained evidence for novel mechanisms of AmB resistance mechanisms and possible fitness compensation mutations.