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Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2
Author(s) -
Yamada Tsuyoshi,
Yaguchi Takashi,
Tamura Takashi,
Pich Christine,
Salamin Karine,
Feuermann Marc,
Monod Michel
Publication year - 2021
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/myc.13286
Subject(s) - trichophyton rubrum , itraconazole , mutant , atp binding cassette transporter , microbiology and biotechnology , voriconazole , drug resistance , terbinafine , biology , transporter , dermatophyte , efflux , gene , antifungal , genetics
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 .