HSAF-induced antifungal effects in Candida albicans through ROS-mediated apoptosis

Abstract

Heat-stable antifungal factor (HSAF) belongs to polycyclic tetramate macrolactams (PTMs), which inhibits many fungal pathogens and is effective in inhibiting <i>Candida albican</i>s (<i>C. albicans</i>). In this study, we found that HSAF induced the apoptosis of <i>Candida albican</i>s SC5314 through inducing the production of reactive oxygen species (ROS). Nevertheless, we validated the efficacy of HSAF against candidiasis caused by <i>C. albicans</i> in a murine model in vivo, and HSAF significantly improved survival and reduced fungal burden compared to vehicles. A molecular dynamics (MD) simulation was also investigated, revealing the theoretical binding mode of HSAF to the β-tubulin of <i>C. albicans</i>. This study first found PTMs-induced fungal apoptosis through ROS accumulation in <i>C. albicans</i> and its potential as a novel agent for fungicides.