論文 - 詳細
| RRC ID | 89072 |
|---|---|
| 著者 | Isozaki Y, Makikawa T, Kimura K, Nishihara D, Fujino M, Tanaka Y, Hayashi C, Ishizaki Y, Igarashi M, Yokoyama T, Toshima K, Takahashi D. |
| タイトル | Creation of a macrolide antibiotic against non-tuberculous Mycobacterium using late-stage boron-mediated aglycon delivery. |
| ジャーナル | Sci Adv |
| Abstract |
Non-tuberculous mycobacteria (NTM) is gaining clinical recognition as a recently emerging pulmonary pathogen. Mycobacterium avium complex (MAC), the most common NTM, is the cause of pulmonary MAC disease. Currently, the macrolide azithromycin (AZM) is the standard first-line antibiotic for treatment of the disease. However, the rise of drug-resistant MAC necessitates the development of alternative therapeutics. Here, we present a late-stage boron-mediated aglycon delivery strategy for selective modification of AZM, generating a library of potential anti-MAC drugs designated KU01 to KU13. Screening of KU01 to KU13 revealed that KU13 exhibited enhanced antimicrobial activity against wild-type and macrolide-resistant MAC compared to AZM. Cryo-electron microscopy analysis indicated that the inserted tercyclic moiety of KU13 formed a robust anchor on the bacterial ribosome, creating a binding pocket with base flipping of U2847, potentially bypassing the standard mechanism of macrolide resistance. These results position KU13 as a promising lead for therapeutics against macrolide-resistant MAC. |
| 巻・号 | 11(10) |
| ページ | eadt2352 |
| 公開日 | 2025-3-7 |
| DOI | 10.1126/sciadv.adt2352 |
| PMID | 40043128 |
| PMC | PMC11881915 |
| MeSH | Anti-Bacterial Agents* / chemistry Anti-Bacterial Agents* / pharmacology Azithromycin / chemistry Azithromycin / pharmacology Boron* / chemistry Cryoelectron Microscopy Drug Resistance, Bacterial / drug effects Humans Macrolides* / chemistry Macrolides* / pharmacology Microbial Sensitivity Tests Mycobacterium avium Complex* / drug effects Nontuberculous Mycobacteria* / drug effects |
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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 | 12 |
| 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 | |
| 一般微生物 | JCM6384 |