Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine

Abstract This study explores the effectiveness of various antifungal drugs in treating sporotrichosis caused by Sporothrix schenckii, especially in non-wild-type (non-WT) strains. The drugs tested include enilconazole (ENIL), isavuconazole (ISA), posaconazole (POS), terbinafine (TER), and itraconazo...

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Main Authors: Vasurom Aroonvuthiphong, Norasuthi Bangphoomi
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87711-3
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author Vasurom Aroonvuthiphong
Norasuthi Bangphoomi
author_facet Vasurom Aroonvuthiphong
Norasuthi Bangphoomi
author_sort Vasurom Aroonvuthiphong
collection DOAJ
description Abstract This study explores the effectiveness of various antifungal drugs in treating sporotrichosis caused by Sporothrix schenckii, especially in non-wild-type (non-WT) strains. The drugs tested include enilconazole (ENIL), isavuconazole (ISA), posaconazole (POS), terbinafine (TER), and itraconazole (ITC). The study involved in vitro and in vivo tests on 10 WT isolates and eight ITC non-WT isolates. Two isolates were assessed using time-kill assays, checkerboard assays, and Galleria mellonella infection models. In vitro studies have shown that all of these drugs were more effective than or equal to ITC against WT and non-WT isolates. No ITC resistance was observed with other azoles. All drugs inhibited fungal growth of WT and non-WT strains within 24 h at all incubations. ENIL and TER showed fungicidal effect against types at over 2x minimum inhibitory concentrations with no regrowth. POS was fungicidal against WT at high concentrations but not against non-WT. ISA was only fungicidal for non-WT. ITC did not exhibit any fungicidal activity. In checkerboard experiments, the combination of POS or ISA with TER showed enhanced activity against WT and non-WT strains, surpassing the combination of ITC with TER. In vivo model experiments demonstrated significantly reduced mortality rates with ENIL, POS, and TER against WT and with ENIL, ISA, POS, and TER against non-WT. The study concludes that monotherapy with ENIL, ISA, POS, and TER, and combinations of POS/TER or ISA/TER, show promise as effective antifungal treatments against S. schenckii, including ITC-non-WT isolates.
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spelling doaj-art-c9f8e731033e4823b9729082a42b4a042025-01-26T12:26:02ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-87711-3Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafineVasurom Aroonvuthiphong0Norasuthi Bangphoomi1Veterinary Biomedical Science Program, Faculty of Veterinary Science, Mahidol UniversityDepartment of Pre-clinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol UniversityAbstract This study explores the effectiveness of various antifungal drugs in treating sporotrichosis caused by Sporothrix schenckii, especially in non-wild-type (non-WT) strains. The drugs tested include enilconazole (ENIL), isavuconazole (ISA), posaconazole (POS), terbinafine (TER), and itraconazole (ITC). The study involved in vitro and in vivo tests on 10 WT isolates and eight ITC non-WT isolates. Two isolates were assessed using time-kill assays, checkerboard assays, and Galleria mellonella infection models. In vitro studies have shown that all of these drugs were more effective than or equal to ITC against WT and non-WT isolates. No ITC resistance was observed with other azoles. All drugs inhibited fungal growth of WT and non-WT strains within 24 h at all incubations. ENIL and TER showed fungicidal effect against types at over 2x minimum inhibitory concentrations with no regrowth. POS was fungicidal against WT at high concentrations but not against non-WT. ISA was only fungicidal for non-WT. ITC did not exhibit any fungicidal activity. In checkerboard experiments, the combination of POS or ISA with TER showed enhanced activity against WT and non-WT strains, surpassing the combination of ITC with TER. In vivo model experiments demonstrated significantly reduced mortality rates with ENIL, POS, and TER against WT and with ENIL, ISA, POS, and TER against non-WT. The study concludes that monotherapy with ENIL, ISA, POS, and TER, and combinations of POS/TER or ISA/TER, show promise as effective antifungal treatments against S. schenckii, including ITC-non-WT isolates.https://doi.org/10.1038/s41598-025-87711-3Sporothrix schenckii.SporotrichosisAntifungalsItraconazole nonwild-typeGalleria mellonella model
spellingShingle Vasurom Aroonvuthiphong
Norasuthi Bangphoomi
Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
Scientific Reports
Sporothrix schenckii.
Sporotrichosis
Antifungals
Itraconazole nonwild-type
Galleria mellonella model
title Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
title_full Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
title_fullStr Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
title_full_unstemmed Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
title_short Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine
title_sort therapeutic alternatives for sporotrichosis induced by wild type and non wild type sporothrix schenckii through in vitro and in vivo assessment of enilconazole isavuconazole posaconazole and terbinafine
topic Sporothrix schenckii.
Sporotrichosis
Antifungals
Itraconazole nonwild-type
Galleria mellonella model
url https://doi.org/10.1038/s41598-025-87711-3
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AT norasuthibangphoomi therapeuticalternativesforsporotrichosisinducedbywildtypeandnonwildtypesporothrixschenckiithroughinvitroandinvivoassessmentofenilconazoleisavuconazoleposaconazoleandterbinafine