Developing new technology for understanding Candida’s tolerance to drugs

Carol Munro & Louise Walker

Candida albicans is the major fungal pathogen of humans, causing life-threatening infections in patients with weakened immune systems. The DNA blueprint of this organism was revealed over a decade ago and provided a huge leap forward in the characterisation of this species. However, we have limited understanding of how the genetic code of this fungus allows it to colonise and invade the human body and tolerate drugs that are used to treat fungal infections.

This project will apply cutting-edge technology to develop an experimental pipeline that will allow us to assess characteristics of mutated versions of this fungus. Each mutant strain will be tagged with a unique molecular signature to allow us to track it within pools that contain a mixture of strains. We can therefore follow the abundance of each strain during competition experiments. We will examine the drug susceptibility of approximately five hundred mutant strains, to determine which mutants are more resistant or more sensitive to an antifungal drug. We have shown in the past that activation of cellular pathways can provide the fungus with the ability to tolerate antifungal drugs, which allows infections to progress even when treatment is applied.

The data generated will allow us to associate particular DNA sequences with the cellular pathways involved in the response to antifungal treatment. In the longer term this knowledge could be applied to designing new therapies by targeting sequences and pathways that give the fungus tolerance to existing drugs.

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