Screening of the pathogen box reveals promising antifungal compound against Cryptococcus and Candida species

Reported by Katrin Braasch, postdoctoral fellow in the Piret lab, Michael Smith Laboratories

Dr. Francois Mayer, a Postdoctoral Fellow in Dr. Jim Kronstad’s research lab, is the lead author on a recent publication in mSphere: “Discovery of a Novel Antifungal Agent in the Pathogen Box”. The study identifies a promising compound from a chemical library with strong antifungal activity against Cryptococcus neoformans and Candida albicans under nutrient-limited conditions. Read the full article here.

Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality, especially in immuno-compromised patients. Currently only a limited number of antifungal drugs are available and increasing resistance further complicates treatments. A major obstacle in the discovery of new drugs is the necessity for the specific activity towards pathogen-unique targets. In addition, it is important for potential compounds to have low toxicity against mammalian cells.

Dr. Mayer states, “the Pathogen Box, led by Medicines for Malaria Venture (Switzerland), is a fantastic open-source drug discovery project that aims to boost drug discovery against neglected diseases”.  The compounds in the Pathogen Box have low toxicity in mammalian cells making them ideal drug candidates. In this study, the chemical library was screened for novel antifungal activity against “Cryptococcus neoformans and Candida albicans, as these two fungi are amongst the most important fungal pathogens of humans” according to Dr. Mayer. The screening identified a novel compound that was highly potent against both fungi under nutrient-limited conditions. This is promising as both C. neoformans and C. albicans are likely exposed to nutrient-limited conditions during infection. The preliminary experiments point to the plasma membrane and cell wall as possible targets of the identified compound.

Dr. Mayer states “the discovery of a novel compound with antifungal activity against both organisms was very exciting and we hope that it may serve as a novel lead compound for antifungal drug development.”