In vitro and in vivo analysis of monotherapy and dual therapy with ethyl caffeate and fluconazole on virulence factors of Candida albicans and systemic candidiasis

Journal of Global Antimicrobial Resistance

Jing Shao¹  Nan Xiao¹  Min Pan²  Ting Cheng³  Tianming Wang⁴  Qirui Wang⁵  Ning Li⁵  Jiadi Wu⁵  Guiming Yan⁵  Daqiang Wu⁵ 

[1] Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Zhijing Building, 350 Longzihu Road, Xinzhan District, Hefei, 230012, Anhui, P.R. China;Laboratory of Infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, 436 Room, Zhijing Building, 350 Longzihu Road, Xinzhan District, 230012, Hefei, P.R. China;Department of Anatomy, School of Basic Medicine, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan District, 430074, Wuhan, P.R. China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, 230032, Hefei, P.R. China;Laboratory of Infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, 436 Room, Zhijing Building, 350 Longzihu Road, Xinzhan District, 230012, Hefei, P.R. China;

关键词: Candida albicans;    Ethyl caffeate;    Fluconazole;    Fungal infection;    Combination;    Synergy;   

DOI  :  

来源: DOAJ

【 摘 要 】

ABSTRACT:Objectives: Candida albicans is the most clinically prevalent cause of systemic fungal infections in the immunocompromised population. The biofilm-forming ability of C. albicans confers resistance to conventional antifungal agents. The main aim of this study was to investigate the antifungal effects of ethyl caffeate (EC) alone and in combination with fluconazole (FLU) against C. albicans isolates. Methods: The single and combined antifungal activities of EC and FLU were evaluated against planktonic and biofilm cells of C. albicans by the checkerboard assay, time–kill test, crystal violet assay, live/dead staining, rhodamine 6G (R6G) efflux analysis and hydrolase activity. Monotherapy and dual therapy of EC and FLU against systemic candidiasis in a mouse model was also evaluated. Results: The results showed that EC+FLU displayed synergism in 14/26 planktonic C. albicans isolates and 11/26 C. albicans biofilms with fractional inhibitory concentration index (FICI) values ranging between 0.06–0.49 and 0.02–0.38, respectively. Compared with monotherapy, the combination of EC+FLU can markedly inhibit adhesion, yeast-to-hyphae transition, premature and mature biofilm metabolism, hydrolase secretion and drug efflux function of C. albicans Z1407 and Z4935. Moreover, EC can potentiate the antifungal activity of FLU to improve mouse survival, reduce fungal burden and alleviate pathological damage in both C. albicans isolates compared with EC or FLU used alone. Conclusion: EC exhibits a moderate antifungal potential but can be a strong synergist with FLU against C. albicans, highlighting the potential of EC in clinical antifungal therapy as a sensitiser.

【 授权许可】

Unknown