論文 - 詳細
| RRC ID | 52832 |
|---|---|
| 著者 | Hagiwara D, Watanabe A, Kamei K. |
| タイトル | Sensitisation of an Azole-Resistant Aspergillus fumigatus Strain containing the Cyp51A-Related Mutation by Deleting the SrbA Gene. |
| ジャーナル | Sci Rep |
| Abstract |
Azoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of cyp51A, and have disseminated globally in a short period of time. In this study, we investigated whether an azole-resistant strain with a 46-bp TR (TR46/Y121F/T289A) could be sensitised to azoles by deletion of srbA, encoding a direct regulator of cyp51A. The loss of SrbA did not affect colony growth or conidia production, but decreased expression of cyp51A. The srbA deletion strain showed hyper-susceptibility to medical azoles as well as azole fungicides, while its sensitivity to non-azole fungicides was unchanged. This is the first demonstration that deletion of a regulator of cyp51A can sensitise an azole-resistant A. fumigatus strain. This finding may assist in the development of new drugs to help combat life-threatening azole-resistant fungal pathogens. |
| 巻・号 | 6 |
| ページ | 38833 |
| 公開日 | 2016-12-9 |
| DOI | 10.1038/srep38833 |
| PII | srep38833 |
| PMID | 27934927 |
| PMC | PMC5146965 |
| MeSH | Antifungal Agents / pharmacology* Aspergillus fumigatus / drug effects* Aspergillus fumigatus / genetics Azoles / pharmacology* Cytochrome P-450 Enzyme System / biosynthesis* Cytochrome P-450 Enzyme System / genetics Drug Resistance, Multiple, Fungal / genetics* Fungal Proteins / biosynthesis Fungal Proteins / genetics* Fungicides, Industrial / pharmacology* Gene Deletion Gene Expression Regulation, Fungal / genetics* Genes, Fungal* Mutation Oxygen / pharmacology Tandem Repeat Sequences Transcription Factors / genetics* |
| IF | 3.998 |
| 引用数 | 9 |
| 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 | 3 |
| 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 | |
| 病原微生物 | |