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

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 antifun...

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Autores principales:	Tianming Wang, Min Pan, Nan Xiao, Jiadi Wu, Qirui Wang, Ting Cheng, Guiming Yan, Daqiang Wu, Ning Li, Jing Shao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Candida albicans Ethyl caffeate Fluconazole Fungal infection Combination Synergy Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bad0a52127a34d07bb28cac1abc3455d
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spelling	oai:doaj.org-article:bad0a52127a34d07bb28cac1abc3455d2021-11-14T04:32:50ZIn vitro and in vivo analysis of monotherapy and dual therapy with ethyl caffeate and fluconazole on virulence factors of Candida albicans and systemic candidiasis2213-716510.1016/j.jgar.2021.10.005https://doaj.org/article/bad0a52127a34d07bb28cac1abc3455d2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213716521002204https://doaj.org/toc/2213-7165ABSTRACT: 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.Tianming WangMin PanNan XiaoJiadi WuQirui WangTing ChengGuiming YanDaqiang WuNing LiJing ShaoElsevierarticleCandida albicansEthyl caffeateFluconazoleFungal infectionCombinationSynergyMicrobiologyQR1-502ENJournal of Global Antimicrobial Resistance, Vol 27, Iss , Pp 253-266 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Ethyl caffeate Fluconazole Fungal infection Combination Synergy Microbiology QR1-502
spellingShingle	Candida albicans Ethyl caffeate Fluconazole Fungal infection Combination Synergy Microbiology QR1-502 Tianming Wang Min Pan Nan Xiao Jiadi Wu Qirui Wang Ting Cheng Guiming Yan Daqiang Wu Ning Li Jing Shao 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
description	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.
format	article
author	Tianming Wang Min Pan Nan Xiao Jiadi Wu Qirui Wang Ting Cheng Guiming Yan Daqiang Wu Ning Li Jing Shao
author_facet	Tianming Wang Min Pan Nan Xiao Jiadi Wu Qirui Wang Ting Cheng Guiming Yan Daqiang Wu Ning Li Jing Shao
author_sort	Tianming Wang
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bad0a52127a34d07bb28cac1abc3455d
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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

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