Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.
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State: Public
Version: Final published version
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Serval ID
serval:BIB_1E13B842E1C3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.
Journal
Mycoses
ISSN
1439-0507 (Electronic)
ISSN-L
0933-7407
Publication state
Published
Issued date
08/2021
Peer-reviewed
Oui
Volume
64
Number
8
Pages
936-946
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.
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.
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.
Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.
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.
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.
Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
Keywords
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, Trichophyton rubrum, ABC transporters, TruMDR2, dermatophytes, itraconazole resistance
Pubmed
Web of science
Create date
11/05/2021 9:47
Last modification date
03/03/2023 7:48
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