Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates

Details

Serval ID
serval:BIB_785913880AAD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates
Journal
Medical Mycology
Author(s)
Favre  B., Ghannoum  M. A., Ryder  N. S.
ISSN
1369-3786 (Print)
Publication state
Published
Issued date
12/2004
Volume
42
Number
6
Pages
525-9
Notes
Comparative Study
Journal Article --- Old month value: Dec
Abstract
We investigated the biochemical basis for resistance in six sequential clinical isolates of Trichophyton rubrum, from the same patient, which exhibited high-level primary resistance to terbinafine. Cellular ergosterol biosynthesis was measured by incorporation of [14C]acetate, and microsomal squalene epoxidase was assayed by conversion of [3H]squalene to squalene epoxide and lanosterol. Direct comparison was made with a terbinafine-susceptible reference strain of T. rubrum in which squalene epoxidase was previously studied. Resistant isolates displayed normal cellular ergosterol biosynthesis, although slight accumulation of radiolabeled squalene suggested reduced squalene epoxidase activity. Ergosterol biosynthesis in the resistant isolates was only inhibited by terbinafine concentrations above 1 microg/ml (IC50 5 microg/ml). In the reference strain, ergosterol biosynthesis was eliminated by terbinafine at 0.03 microg/ml in accordance with historical data. There was no significant difference in sensitivity between the six resistant isolates. Squalene epoxidase from resistant strains was three orders of magnitude less sensitive than normal enzyme to terbinafine (IC50 of 30 micromol/l and 19 n mol/l respectively). The epoxidase in the resistant strains was also unresponsive to tolnaftate. Resistance to terbinafine in these T. rubrum isolates appears to be due to alterations in the squalene epoxidase gene or a factor essential for its activity.
Keywords
Antifungal Agents/pharmacology *Drug Resistance, Fungal Ergosterol/biosynthesis Humans Naphthalenes/*pharmacology Oxygenases/metabolism Squalene Monooxygenase Tolnaftate/pharmacology Trichophyton/*drug effects/isolation & purification/*metabolism
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 17:32
Last modification date
20/08/2019 15:35
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