Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point Mutations in the Squalene Epoxidase Gene.

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: Final published version
Serval ID
serval:BIB_80F57BC27CF5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point Mutations in the Squalene Epoxidase Gene.
Journal
Antimicrobial agents and chemotherapy
Author(s)
Yamada T., Maeda M., Alshahni M.M., Tanaka R., Yaguchi T., Bontems O., Salamin K., Fratti M., Monod M.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
07/2017
Peer-reviewed
Oui
Volume
61
Number
7
Pages
1-13
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Terbinafine is one of the allylamine antifungal agents whose target is squalene epoxidase (SQLE). This agent has been extensively used in the therapy of dermatophyte infections. The incidence of patients with tinea pedis or unguium tolerant to terbinafine treatment prompted us to screen the terbinafine resistance of all javax.xml.bind.JAXBElement@dc06fb4 clinical isolates from the laboratory of the Centre Hospitalier Universitaire Vaudois collected over a 3-year period and to identify their mechanism of resistance. Among 2,056 tested isolates, 17 (≈1%) showed reduced terbinafine susceptibility, and all of these were found to harbor javax.xml.bind.JAXBElement@374d721c gene alleles with different single point mutations, leading to single amino acid substitutions at one of four positions (Leu javax.xml.bind.JAXBElement@4655f570 , Phe javax.xml.bind.JAXBElement@112b804a , Phe javax.xml.bind.JAXBElement@1f18e014 , and His javax.xml.bind.JAXBElement@4319ac79 ) of the SQLE protein. Point mutations leading to the corresponding amino acid substitutions were introduced into the endogenous javax.xml.bind.JAXBElement@2a0e3f1f gene of a terbinafine-sensitive javax.xml.bind.JAXBElement@67eac3c4 (formerly javax.xml.bind.JAXBElement@3f2a876d ) strain. All of the generated javax.xml.bind.JAXBElement@315e9e95 transformants expressing mutated SQLE proteins exhibited obvious terbinafine-resistant phenotypes compared to the phenotypes of the parent strain and of transformants expressing wild-type SQLE proteins. Nearly identical phenotypes were also observed in javax.xml.bind.JAXBElement@6af3a966 transformants expressing mutant forms of javax.xml.bind.JAXBElement@5bb6b31f SQLE proteins. Considering that the genome size of dermatophytes is about 22 Mb, the frequency of terbinafine-resistant clinical isolates was strikingly high. Increased exposure to antifungal drugs could favor the generation of resistant strains.

Keywords
Antifungal Agents/pharmacology, Arthrodermataceae/drug effects, Arthrodermataceae/enzymology, Arthrodermataceae/genetics, Drug Resistance, Fungal/genetics, Microbial Sensitivity Tests, Naphthalenes/pharmacology, Point Mutation/genetics, Squalene Monooxygenase/genetics, Trichophyton/drug effects, Trichophyton/enzymology, Trichophyton/genetics, Trichophyton, antifungal resistance, dermatophytes, reverse genetics approach, squalene epoxidase, terbinafine
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2017 19:36
Last modification date
20/08/2019 15:41
Usage data