Identification of a new antifungal compound with a novel mode-of-action derived from microbial dark matter

Mortality associated with fungal infections already exceeds malaria

casualties threefold. Due to an ever-rising immunocompromised

population, these figures will only continue to increase. Being

eukaryotic, fungi share many biological processes with humans,

making toxicity a huge issue during drug development. Currently,

there are only five antifungal drug classes available. Each class with

their distinct mode of action to kill pathogenic fungal cells or inhibit

further fungal cell growth. However, resistance of pathogenic species

has become alarming, causing an increasing need for novel drugs.

By allowing the micro-organisms to first grow in their natural habitat,

our lab succeeded in growing micro-organisms which normally do not

prosper in laboratory growth conditions. Many of these strains were

found to have antifungal activity against Candida albicans, one of the

more notorious opportunistic fungal pathogens. Moreover, our initial

tests indicate that they could work via a novel mechanic, different

from the already established antifungal drug classes. This research

aims to identify and purify responsible antifungal compounds.

Further, we wish to undertake mode of action studies to possibly

identify a novel antifungal drug class. If successful, not only will we

be left with a lead compound for antifungal drug development, but

also provide evidence that there are still antifungal natural products

waiting to be discovered.