From Challenge to Opportunity: Multidrug Resistance and Collateral Sensitivity in Human Fungal Pathogens

Uncovering genetic mechanisms to develop treatments combating multidrug-resistant fungal infections

Clinical mycology

Summary

This research investigates how Candida species develop resistance to antifungal drugs and explores whether resistance to one drug increases susceptibility to another (collateral sensitivity). It aims to uncover genetic mechanisms and develop new treatment strategies to combat multidrug-resistant fungal infections.

How are we doing it?

We will expose Candida strains to increasing concentrations of antifungal drugs to generate resistant populations, then test them for cross-resistance and collateral sensitivity. Genetic differences between resistant and sensitive strains will be analysed using Next-Generation Sequencing. Computational tools will help map resistance pathways, and imaging will assess drug impact on fungal cell walls. Together, these methods will reveal how resistance arises and guide new treatment strategies.

What happens next?

In the short term, this project will identify key genes involved in antifungal resistance and collateral sensitivity in Candida species, improving diagnostics and treatment choices. Long term, it could enable drug cycling or combination therapies and support the development of new antifungal drugs. The findings aim to guide clinical practices, reduce resistance, and improve global patient outcomes.

Funding

NIHR Exeter BRC