Evaluation of the efficacy of heat shock protein inhibitors and antifungal drug combinations against Candida spp.

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dc.authoridDağ, İlknur/0000-0002-7352-8653
dc.contributor.authorKiraz, Nuri
dc.contributor.authorKaya, Sümeyye Sen
dc.contributor.authorÖz, Yasemin
dc.contributor.authorDağ, İlknur
dc.date.accessioned2023-05-06T17:23:36Z
dc.date.available2023-05-06T17:23:36Z
dc.date.issued2023
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Mikrobiyoloji Ana Bilim Dalı
dc.description.abstractCandida species are one of the predominant causes of fungal infections and show drug-resistant infections in immune-compromised individuals. Simultaneous targeting of existing antifungal drugs with heat shock protein 90 (Hsp90) inhibitors may be an approach that increases the efficacy of antifungal drugs. Also, since most of the patients at risk for invasive fungal infections use these anticancer or immunosuppressive drugs, synergistic interaction in combination treatment can reduce the dose of antifungal drugs and create an alternative for the toxicity problem. In this study, in vitro efficacy of commonly used antifungals (amphotericin B, caspofungin, itraconazole, voriconazole, and fluconazole) in combination with four heat shock protein inhibitors geldanamycin, 17-allylamino-17-demethoxygeldanamycin, radicicol, and novobiocin against 30 clinical Candida isolates (C. albicansn = 13, C. krusein = 7, and C. glabratan = 10) were evaluated by time kill and checkerboard methods. The significant synergistic interaction determined especially in the combinations of geldanamycin with antifungal drugs suggests that substances with inhibitory effects on Hsp90 increase the effectiveness of antifungals or reduce the antifungal resistance. Although Hsp90 inhibitors alone did not have any significant antifungal activity, they did not show adverse interactions in combination with antifungals, and at some concentrations, they increased the effectiveness of the antifungals. These in vitro results have been found promising for the development of new therapeutic approaches in the treatment of invasive fungal infections. However, detailed studies are needed.
dc.description.sponsorshipTUBITAK [112S503]
dc.description.sponsorshipThis work was supported by a grant from TUBITAK (Project No. 112S503).
dc.identifier.doi10.1007/s12210-022-01118-0
dc.identifier.endpage188
dc.identifier.issn2037-4631
dc.identifier.issn1720-0776
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85144367937
dc.identifier.scopusqualityQ2
dc.identifier.startpage179
dc.identifier.urihttps://doi.org/10.1007/s12210-022-01118-0
dc.identifier.urihttps://hdl.handle.net/20.500.11776/12182
dc.identifier.volume34
dc.identifier.wosWOS:000900881300005
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorKiraz, Nuri
dc.language.isoen
dc.publisherSpringer-Verlag Italia Srl
dc.relation.ispartofRendiconti Lincei-Scienze Fisiche E Naturali
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAntifungal susceptibility
dc.subjectCandida
dc.subjectHsp90 inhibitors
dc.subjectCombination therapy
dc.subjectCryptococcus-Neoformans
dc.subjectHsp90 Inhibitor
dc.subjectTime-Kill
dc.subjectIn-Vitro
dc.subjectResistance
dc.subjectVoriconazole
dc.subjectCaspofungin
dc.subjectFluconazole
dc.subjectVirulence
dc.titleEvaluation of the efficacy of heat shock protein inhibitors and antifungal drug combinations against Candida spp.
dc.typeArticle

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