Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.
Trichophyton rubrum
ABC transporters
TruMDR2
dermatophytes
itraconazole resistance
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
revised:
28
03
2021
received:
28
02
2021
accepted:
07
04
2021
pubmed:
26
4
2021
medline:
16
11
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.
METHODS
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
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
CONCLUSIONS
Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B
0
Antifungal Agents
0
Itraconazole
304NUG5GF4
Banques de données
GENBANK
['M12304', 'X02390', 'MK787243', 'EAL84894', 'MK787262']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
936-946Subventions
Organisme : Joint Usage/Research Program of the Medical Mycology Research Center, Chiba University
ID : 20-10
Informations de copyright
© 2021 Wiley-VCH GmbH.
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