論文 - 詳細
| RRC ID | 53581 |
|---|---|
| 著者 | Cho H, Uehara T, Bernhardt TG. |
| タイトル | Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. |
| ジャーナル | Cell |
| Abstract |
Penicillin and related beta-lactams comprise one of our oldest and most widely used antibiotic therapies. These drugs have long been known to target enzymes called penicillin-binding proteins (PBPs) that build the bacterial cell wall. Investigating the downstream consequences of target inhibition and how they contribute to the lethal action of these important drugs, we demonstrate that beta-lactams do more than just inhibit the PBPs as is commonly believed. Rather, they induce a toxic malfunctioning of their target biosynthetic machinery involving a futile cycle of cell wall synthesis and degradation, thereby depleting cellular resources and bolstering their killing activity. Characterization of this mode of action additionally revealed a quality control function for enzymes that cleave bonds in the cell wall matrix. The results thus provide insight into the mechanism of cell wall assembly and suggest how best to interfere with the process for future antibiotic development. |
| 巻・号 | 159(6) |
| ページ | 1300-11 |
| 公開日 | 2014-12-4 |
| DOI | 10.1016/j.cell.2014.11.017 |
| PII | S0092-8674(14)01448-2 |
| PMID | 25480295 |
| PMC | PMC4258230 |
| MeSH | Amdinocillin / pharmacology* Anti-Bacterial Agents / pharmacology* Cell Wall / drug effects Cell Wall / enzymology Escherichia coli / cytology Escherichia coli / drug effects* Escherichia coli / enzymology Glycoside Hydrolases / antagonists & inhibitors Penicillin-Binding Proteins / metabolism Peptidoglycan / metabolism beta-Lactams / pharmacology* |
| IF | 38.637 |
| 引用数 | 197 |
| リソース情報 | |
| 原核生物(大腸菌) | |