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Project

Exploration and validation of riboflavin synthesis as a novel target for antifungal drugs

Nearly one billion people worldwide suffer from fungal infections and this number is increasing vastly due to a growing population of immunocompromised patients. Invasive fungal infections are accompanied with high mortality rates exceeding that of malaria and breast cancer. Finding new antifungal drug targets is challenging due to the high conservation between fungi and humans, as both are eukaryotes. A pathway that is promising in this respect is riboflavin synthesis. Riboflavin or vitamin B2 is essential in all organisms. However, while fungi possess the necessary biosynthesis machinery for endogenous production, humans do not. Therefore, drugs targeting these fungal riboflavin synthesis enzymes will have limited host toxicity. Preliminary data generated by our laboratory has highlighted the potential of riboflavin as an antifungal drug target. Deletion of Rib1, an enzyme involved in riboflavin synthesis, renders the strain completely avirulent in a systemic mouse model. In this project we will explore this pathway in greater detail in order to uncover interesting molecular drug targets. We will also extrapolate our findings to emerging multi-drug resistant non-albicans Candida species: C. glabrata and C. auris, as these represent a particulate obstacle to current medicine. Based on a well thought-out cellular screening, we aim to develop a new lead compound with a novel mode-of-action that, in the long term, has the potential to be transformed into a market-ready drug.

Date:27 Oct 2020 →  Today
Keywords:Antifungal drug development, Riboflavin synthesis, Candida infection
Disciplines:Mycology, Proteins
Project type:PhD project