論文 - 詳細
| RRC ID | 52787 |
|---|---|
| 著者 | Toh-E A, Ohkusu M, Shimizu K, Yamaguchi M, Ishiwada N, Watanabe A, Kamei K. |
| タイトル | Creation, characterization and utilization of Cryptococcus neoformans mutants sensitive to micafungin. |
| ジャーナル | Curr Genet |
| Abstract |
We constructed deletion mutants of Cryptococcus neoformans var neoformans (serotype D) genes encoding late ergosterol biosynthetic pathway enzymes and found that the mutations enhanced susceptibility to various drugs including micafungin, one of the echinocandins, to which wild-type Cryptococcus strains show no susceptibility. Furthermore, through isolation of a mutant resistant to micafungin from a micafungin-sensitive erg mutant and genetic analysis of it, we found that the responsible mutation occurred in the hotspot 2 of FKS1 encoding β-1, 3-glucan synthase, indicating that micafungin inhibited the growth of the erg mutant via inhibiting Fks1 activity. Addition of ergosterol to the culture of the erg mutants recovered the resistance to micafungin, suggesting that the presence of ergosterol in membrane inhibits the accession of micafungin to its target. We found that a loss of one of genes encoding subunits of v-ATPase, VPH1, made Cryptococcus cells sensitive to micafungin. Our observation that the erg2 vph1 double mutant was more sensitive to micafungin than either single mutant suggests that these two genes act differently in becoming resistant to micafungin. The erg mutants allowed us to study the physiological significance of β-1, 3-glucan synthesis in C. neoformans; the inhibition of β-1, 3-glucan synthesis induced cell death and changes in cellular morphology. By observing the erg mutant cells recovering from the growth inhibition imposed by micafungin, we recognized β-1, 3-glucan synthesis would suppress filamentous growth in C. neoformans. |
| 巻・号 | 63(6) |
| ページ | 1093-1104 |
| 公開日 | 2017-12-1 |
| DOI | 10.1007/s00294-017-0713-8 |
| PII | 10.1007/s00294-017-0713-8 |
| PMID | 28560585 |
| MeSH | Antifungal Agents / pharmacology Cryptococcus neoformans / drug effects Cryptococcus neoformans / enzymology Cryptococcus neoformans / genetics* Cryptococcus neoformans / growth & development Drug Resistance, Fungal / genetics* Echinocandins / pharmacology* Ergosterol / biosynthesis Ergosterol / pharmacology Fungal Proteins / genetics Fungal Proteins / metabolism Gene Expression Regulation, Fungal* Genetic Engineering Glucosyltransferases / deficiency Glucosyltransferases / genetics* Lipopeptides / pharmacology* Micafungin Microbial Sensitivity Tests Mutation Protein Subunits / deficiency Protein Subunits / genetics Vacuolar Proton-Translocating ATPases / deficiency Vacuolar Proton-Translocating ATPases / genetics* |
| IF | 3.464 |
| 引用数 | 2 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | 病原真菌：IFM 63013 |