2. Academic Validation
  3. Synergy and Mechanism of Leflunomide Plus Fluconazole Against Resistant Candida albicans: An in vitro Study

Synergy and Mechanism of Leflunomide Plus Fluconazole Against Resistant Candida albicans: An in vitro Study

  • Infect Drug Resist. 2023 Jun 27;16:4147-4158. doi: 10.2147/IDR.S415229.
Xiuyun Li 1 2,  Ning Zhang 1,  Liuping Zhang 3,  Chang Liu 4,  Shicun Zheng # 1,  Hongxiang Lou # 2
Affiliations

Affiliations

  • 1 Maternal and Child Health Development Research Center, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong Province, 250014, People's Republic of China.
  • 2 Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250012, People's Republic of China.
  • 3 Pharmaceutical Department, Shanxian Central Hospital, Heze, Shandong Province, 274300, People's Republic of China.
  • 4 Hospital for Reproductive Medicine Affiliated to Shandong University, Jinan, Shandong Province, 250021, People's Republic of China.
  • # Contributed equally.
PMID: 37396066 DOI: 10.2147/IDR.S415229
Abstract

Objective: The global rise in the resistance of Candida albicans to conventional antifungals makes Candida albicans infections harder to treat. The main objective of this study was to investigate the Antifungal effects and underlying mechanisms of leflunomide in combination with triazoles against resistant Candida albicans.

Methods: In this study, the microdilution method was used to determine the Antifungal effects of leflunomide in combination with three triazoles on planktonic cells in vitro. The morphological transition from yeast to hyphae was observed under a microscope. The effects on ROS, metacaspase, efflux pumps, and intracellular calcium concentration were investigated, respectively.

Results: Our findings suggested that leflunomide + triazoles showed a synergistic effect against resistant Candida albicans in vitro. Further study concluded that the synergistic mechanisms were resulted from multiple factors, including the inhibited efflux of triazoles, the inhibition of yeast-to-hyphae transition, ROS increasing, metacaspase activation, and [Ca2+]i disturbance.

Discussion: Leflunomide appears to be a potential enhancer of current Antifungal agents for treating candidiasis caused by resistant Candida albicans. This study can also serve as an example to inspire the exploration of new approaches to treating resistant Candida albicans.

Keywords

Candida albicans; leflunomide; synergistic mechanism; synergy; triazoles.

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