期刊
FEMS YEAST RESEARCH
卷 21, 期 3, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/femsyr/foab016
关键词
Candida; Cryptococcus; amphotericin B; rimonabant; synergistic antifungal action
资金
- National Natural Science Foundation of China [81903674, 81773786, 81630093]
- Young Scholars Program of Shandong University [2017WLJH41]
- Natural Science Fund for Excellent Young Scholars of Shandong Province of China [ZR2020YQ63]
Amphotericin B is effective against fungi but can cause severe side effects. Combining it with the anti-obesity drug rimonabant shows synergistic antifungal action, reducing toxicity and enhancing fungicidal activity. This combination therapy may have potential for treating fungal infections.
Amphotericin B (AmB) is a very effective antifungal agent, and resistance in clinical isolates is rare. However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB-rimonabant polytherapies for fungal infections.
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