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2 noviembre 2023 @ 16:00 - 17:30
How in vitro multidrug resistance evolution studies with Candida auris not only provide insight in resistance mechanisms, but also in possible treatment options
Speaker: Prof. Patrick Van Dijck
Group Leader – Molecular Biotechnology of Plants and Micro-organisms, Department of Biology, KU Leuven, Leuven, Belgium.
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.