Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi

IntroductionChromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug tre...

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Main Authors: Lulu An, Gengpei Jia, Jingwen Tan, Lianjuan Yang, Yuemei Wang, Lei Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1131416/full
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author Lulu An
Gengpei Jia
Jingwen Tan
Lianjuan Yang
Yuemei Wang
Lei Li
author_facet Lulu An
Gengpei Jia
Jingwen Tan
Lianjuan Yang
Yuemei Wang
Lei Li
author_sort Lulu An
collection DOAJ
description IntroductionChromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition.MethodsIn this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates.ResultsThese analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC.DiscussionOverall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.
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spelling doaj.art-fee3fee6679a4878982125876125af322023-02-23T12:48:33ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-02-011310.3389/fcimb.2023.11314161131416Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungiLulu An0Gengpei Jia1Jingwen Tan2Lianjuan Yang3Yuemei Wang4Lei Li5Department of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of General Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, ChinaDepartment of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shibei Hospital, Shanghai, ChinaDepartment of Clinical Laboratory, Shibei Hospital, Shanghai, ChinaIntroductionChromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition.MethodsIn this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates.ResultsThese analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC.DiscussionOverall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1131416/fulleverolimussynergistic effectchromoblastomycosisantifungaldematiaceous fungi
spellingShingle Lulu An
Gengpei Jia
Jingwen Tan
Lianjuan Yang
Yuemei Wang
Lei Li
Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
Frontiers in Cellular and Infection Microbiology
everolimus
synergistic effect
chromoblastomycosis
antifungal
dematiaceous fungi
title Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
title_full Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
title_fullStr Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
title_full_unstemmed Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
title_short Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
title_sort analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi
topic everolimus
synergistic effect
chromoblastomycosis
antifungal
dematiaceous fungi
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1131416/full
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