RRC ID 67278
著者 Yamada T, Yaguchi T, Tamura T, Pich C, Salamin K, Feuermann M, Monod M.
タイトル Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.
ジャーナル Mycoses
Abstract BACKGROUND:Dermatophytes showing reduced sensitivity to antifungal agents have emerged in several countries. One terbinafine resistant strain of Trichophyton rubrum, TIMM20092, also showed reduced sensitivity to itraconazole (ITC) and voriconazole (VRC). The expression of two genes (TruMDR2 and TruMDR3) encoding multidrug transporters of the ABC family was found to be highly up-regulated in this strain. Deletion of TruMDR3 in TIMM20092 abolished its resistance to VRC but only slightly reduced its resistance to ITC.
OBJECTIVES:We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.
METHODS:The deletion of TruMDR2 by gene replacement was performed in TIMM20092 and one TruMDR3-lacking mutant (∆TruMDR3) previously generated from TIMM20092. TruMDR2 single and TruMDR2/TruMDR3 double mutants (∆TruMDR2 and ∆TruMDR2/3) were successfully obtained, respectively.
RESULTS:The suppression of TruMDR2 was shown to abolish resistance to ITC in TIMM20092 and the TruMDR3-lacking mutant, strongly suggesting that TruMDR2 is a major contributor to ITC resistance in TIMM20092.
CONCLUSIONS:Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
巻・号 64(8)
ページ 936-946
公開日 2021-8-1
DOI 10.1111/myc.13286
PMID 33896045
MeSH ATP Binding Cassette Transporter, Subfamily B / genetics* ATP Binding Cassette Transporter, Subfamily B / metabolism* Antifungal Agents / pharmacology* Arthrodermataceae / drug effects* Arthrodermataceae / genetics* Drug Resistance, Fungal / genetics* Humans Itraconazole / pharmacology* Microbial Sensitivity Tests
IF 3.575
リソース情報
病原真核微生物 Trichophyton rubrum IFM 65860, IFM66825, IFM 66345