HSAF-induced antifungal effects inCandida albicansthrough ROS-mediated apoptosis.
Heat-stable antifungal factor (HSAF) belongs to polycyclic tetramate macrolactams (PTMs), which inhibits many fungal pathogens and is effective in inhibitingCandida albicans (C. albicans). In this study, we found that HSAF induced the apoptosis ofCandida albicans SC5314 through inducing the production of reactive oxygen species (ROS). Nevertheless, we validated the efficacy of HSAF against candidiasis caused byC. albicansin 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 ofC. albicans. This study first found PTMs-induced fungal apoptosis through ROS accumulation inC. albicansand its potential as a novel agent for fungicides.
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China.
Yanjiao
Y
Ding
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China.
Zhenyu
Z
Li
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China.
Yaoyao
Y
Li
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China.
Chunhua
C
Lu
State Key laboratory of Microbial Technology, Shandong University, No. 27 South Shanda Road, Jinan, Shandong 250100, P. R. China.
Haoxin
H
Wang
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P. R. China; State Key laboratory of Microbial Technology, Shandong University, No. 27 South Shanda Road, Jinan, Shandong 250100, P. R. China.
Yuemao
Y
Shen
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Liangcheng
L
Du
Candida albicans; HSAF; apoptosis; reactive oxygen species