biostudies-literatureCarolus HEuropean Research CouncilEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)2954-2969https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618254biostudies-literatureUnknown9(11)Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches.Nature microbiologyCollateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris.PMC7618254951475945352Lagrou KCarolus HBiriukov VSofras DJacobs SBoccarella GVantyghem IBerman JVan Dijck PVerbeeck Tvan den Berg PChen AGoossens LGabaldon TPierson SLobo Romero CSteenackers HfalseCollateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris.Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches.2024-01-01T00:00:00Z2024 Nov2026-06-04T10:32:35.261Z2026-06-02T03:07:42.176ZS-EPMC76182543947269610.1038/s41564-024-01811-w