A new study reveals that azoles, the most widely-used antifungals, cause fungal pathogens to self-destruct by triggering cellular “suicide” programs. This discovery, which details how azoles inhibit ergosterol production leading to cell death through mechanisms like apoptosis and macroautophagy, offers new insights that could help manage resistance and improve strategies for protecting food security and human health. Credit: SciTechDaily.
Scientists have found that the world’s most commonly used class of antifungals causes pathogens to self-destruct. This discovery, led by the University of Exeter, could enhance methods to safeguard food security and protect human health. Azoles target enzymes in the pathogen cell that produce cholesterol-like molecules, named ergosterol. Ergosterol is an important component of cellular bio-membranes. Azoles deplete ergosterol, which results in the killing of the pathogen cell. However, despite the importance of azoles, scientists know little about the actual cause of pathogen death., University of Exeter scientists have uncovered the cellular mechanism by which azoles kill pathogenic fungi.
Lead author Professor Gero Steinberg, who holds a Chair in Cell Biology and is Director of the Bioimaging Centre at the University of Exeter, said: “Our findings rewrite common understanding of how azoles kill fungal pathogens. We show that azoles trigger cellular “suicide” programs, which result in the pathogen self-destructing. This cellular reaction occurs after two days of treatment, suggesting that cells reach a “point of no return” after some time of exposure to azoles.