The Impact of the proton-pump Pma1 inhibition on C. albicans virulence and immune escape

Fungal infections are an escalating global health concern, particularly among immunocompromised individuals, and are intensified by rising antifungal resistance, the emergence of new multi-drug resistant fungal species, and limited therapeutic options. Driven by this collaboration, partners at the university of Copenhagen developed novel antifungal agents targeting Pma1, a highly conserved and essential membrane protein in pathogenic fungi such as Candida albicans and Candida auris, both listed as critical threats by the WHO. In this project, I will evaluate how these innovative classes of antifungal compounds selectively inhibit fungal Pma1 without harming human cells. We will use In vitro infection models together with high-throughput live-cell imaging to evaluate the impact of the Pma1 inhibitors on fungal viability, pathogenicity towards host tissues relevant for mucosal as well as systemic candidiasis. Moreover, I will investigate how these drug candidates shape interactions of C. albicans with immune cells. Fungal pathogenicity is not solely determined by microbial growth, but also by the ability of the pathogen to damage host tissues and evade immune recognition. Therefore, we are eager to assess how the antifungal candidates impact both virulence traits and host–pathogen interactions at the same time. The inhibition of fungal growth will be monitored simultaneously with host cell viability, allowing us to assess whether Pma1 inhibitors represent anti-Infectives or anti-Virulence therapies, and exclude toxicity towards host tissues. Further, we will use our group's Organ-on-chip models established for C. albicans infection (liver and vaginal mucosa) to assess the possible antifungal and anti-virulence effects in a more physiological setting. The project targets an unmet critical clinical need and has the potential to shift the paradigm in antifungal therapy by providing a novel class of antifungal drugs. It will not only deliver promising lead compounds for clinical development but also establish a broadly applicable discovery and evaluation platform for novel antimicrobial agents.

PhD start: 01/01/2026