A mechanism study on the synergistic effects of rifapentine and fluconazole against fluconazole-resistant Candida albicans in vitro

Yulian Wang; Yufei He; Tongkai Cai; Zhongwei Lei; Wenzhi Lei; Yongbing Cao; Jianhua Wu

Heliyon (Mar 2024)

A mechanism study on the synergistic effects of rifapentine and fluconazole against fluconazole-resistant Candida albicans in vitro

Yulian Wang,
Yufei He,
Tongkai Cai,
Zhongwei Lei,
Wenzhi Lei,
Yongbing Cao,
Jianhua Wu

Affiliations

Yulian Wang: Department of Dermatology, Changhai Hospital, Naval Medical University, Shanghai, China
Yufei He: Department of Dermatology, Changhai Hospital, Naval Medical University, Shanghai, China
Tongkai Cai: Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Zhongwei Lei: Department of Rehabilitation, Changhai Hospital, Naval Medical University, Shanghai, China
Wenzhi Lei: Department of Dermatology, Changzheng Hospital, Naval Medical University, Shanghai, China; Corresponding author.
Yongbing Cao: Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author.
Jianhua Wu: Department of Dermatology, Changhai Hospital, Naval Medical University, Shanghai, China; Corresponding author.

Journal volume & issue: Vol. 10, no. 6
p. e27346

Abstract

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Candida albicans (C. albicans) is one of the most common clinical isolates of systemic fungal infection. Long-term and inappropriate use of antifungal drugs can cause fungal resistance, which poses a great challenge to the clinical treatment of fungal infections. The combination of antifungal drugs and non-antifungal drugs to overcome the problem of fungal resistance has become a research hotspot in recent years. Our previous study found that the combination of rifapentine (RFT) and fluconazole (FLC) has a significant synergistic against FLC-resistant C. albicans. The present study aimed to further verify the synergistic effect between FLC and RFT against the FLC-resistant C. albicans 100, and explore the underlying mechanism. The growth curve and spot assay test not only showed the synergistic effect of FLC and RFT on FLC-resistant C. albicans in vitro but exhibited a dose-dependent effect on RFT, indicating that RFT may play a principal role in the synergic effect of the two drugs. Flow cytometry showed that the combined use of RFT and FLC arrested cells in the G2/M phase, inhibiting the normal division and proliferation of FLC-resistant C. albicans. Transmission electron microscopy (TEM) demonstrated that FLC at a low concentration could still cause a certain degree of damage to the cell membrane in the FLC-resistant C. albicans, as represented by irregular morphologic changes and some defects observed in the cell membrane. When FLC was used in combination with RFT, the nuclear membrane was dissolved and the nucleus was condensed into a mass. Detection of the intracellular drug concentration of fungi revealed that the intracellular concentration of RFT was 31–195 fold that of RFT alone when it was concomitantly used with FLC. This indicated that FLC could significantly increase the concentration of RFT in cells, which may be due to the damage caused to the fungal cell membrane by FLC. In short, the present study revealed a synergistic mechanism in the combined use of RFT and FLC, which may provide a novel strategy for the clinical treatment of FLC-resistant C. albicans.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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