Discoveries & Impact (August 2024)
Fungal infections are rapidly becoming a global health threat due to the alarming rise of multidrug-resistant fungal pathogens. This growing resistance undermines the effectiveness of existing therapies and underscores the urgent need for new therapeutic approaches.
A new study led by Jae-Yeon Choi, PhD, in the laboratory of Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and of microbial pathogenesis, uncovers a new cellular process that links the metabolism of vitamin B5 to the ability of fungi to detoxify drugs.
The researchers identified a new pathway in fungi, dubbed the PCA pathway, which involves the biosynthesis of Co-enzyme A and Acetyl-CoA from vitamin B5. The research team demonstrated that genetic disruption of the PCA pathway in fungi markedly increases their vulnerability to a broad spectrum of approved antifungal drugs.
Moreover, the team discovered two drugs (PZ-2891 and AR-12) that recapitulate this genetic alteration, effectively modulating the PCA pathway to enhance the effectiveness of existing therapies.
These findings represent a significant leap in our understanding of fungal resistance mechanisms and herald new treatment possibilities for combating resilient fungal strains, with far-reaching implications for patients worldwide. This research is being further developed at Curatix, a spin-off company from the Ben Mamoun Lab.
To learn more, read the article: “Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi.”
Choi JY, Gihaz S, Munshi M, Singh P, Vydyam P, Hamel P, Adams EM, Sun X, Khalimonchuk O, Fuller K, Ben Mamoun C. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Commun Biol. 2024 Jul 23;7(1):894. doi: 10.1038/s42003-024-06595-7. PMID: 39043829.