Diverse antifungal potency of terbinafine as a therapeutic agent against Exophiala dermatitidis in vitro

Autor: Tomofumi Nakamura, Tatsuya Yoshinouchi, Mayu Okumura, Toshiro Yokoyama, Daisuke Mori, Hirotomo Nakata, Jun-ichirou Yasunaga, Yasuhito Tanaka
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-78815-3
Popis: Abstract Exophiala dermatitidis (E. dermatitidis), which causes skin or respiratory disease, is occasionally fatal in immunocompromised patients. Here, we report the unique antifungal potency of terbinafine (TRB), which targets squalene epoxidase, against E. dermatitidis (SQLEED) using various in vitro approaches. The versatile antifungal activities, including fungicidal activity, biofilm formation inhibition, biofilm eradication activity, and the combination effect of TRB, posaconazole (PSC), and amphotericin B (AmB) with great antifungal potency against E. dermatitidis were evaluated using crystal violet and cell viability assay. TRB formed an H-bond through Y102 in SQLEED in the binding model. E. dermatitidis hyphae elongated and attached to a cell scaffold, forming a membrane-like biofilm. TRB and PSC showed more potent antibiofilm activities than AmB, and exhibited post-antifungal effects without incubation against E. dermatitidis conidia, reducing growth at lower concentrations. In contrast, AmB exhibited strong dose- and time-dependent killing and biofilm-eradication activities. The combination of TRB and PSC was more effective than that of TRB and AmB or PSC and AmB. Although the tissue migration of TRB must be considered, these data suggest that TRB and PSC may be useful agents and a potent combination in severely immunocompromised patients with refractory and systemic E. dermatitidis infection.
Databáze: Directory of Open Access Journals
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