論文 - 詳細
| RRC ID | 81034 |
|---|---|
| 著者 | Ishii M, Yamada T, Ishikawa K, Ichinose K, Monod M, Ohata S. |
| タイトル | The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum. |
| ジャーナル | Antimicrob Agents Chemother |
| Abstract |
The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes. |
| 巻・号 | 68(5) |
| ページ | e0160923 |
| 公開日 | 2024-5-2 |
| DOI | 10.1128/aac.01609-23 |
| PMID | 38567956 |
| PMC | PMC11064548 |
| MeSH | Antifungal Agents* / pharmacology Arthrodermataceae* / drug effects Arthrodermataceae* / genetics Drug Resistance, Fungal* / genetics Fungal Proteins / genetics Fungal Proteins / metabolism Microbial Sensitivity Tests* Phosphorylation Proton-Translocating ATPases / genetics Proton-Translocating ATPases / metabolism Saccharomyces cerevisiae* / drug effects Saccharomyces cerevisiae* / genetics Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism Terbinafine* / pharmacology |
| IF | 4.904 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 病原真核微生物 | Trichophyton rubrum TIMM20092 (= IFM 65860), TIMM20093 (= IFM 65861), TIMM20094 (= IFM 65862) |