論文 - 詳細
| RRC ID | 79175 |
|---|---|
| 著者 | Tomonori Kano, Kazuya Ishikawa, Kazuyuki Furuta, Chikara Kaito |
| タイトル | Knockout of adenylosuccinate synthase purA increases susceptibility to colistin in Escherichia coli |
| ジャーナル | FEMS Microbiology Letters |
| Abstract |
Colistin is a cationic cyclic antimicrobial peptide used as a last resort against multidrug-resistant gram-negative bacteria. To understand the factors involved in colistin susceptibility, we screened colistin-sensitive mutants from an E. coli gene-knockout library (Keio collection). The knockout of purA, whose product catalyzes the synthesis of adenylosuccinate from IMP in the de novo purine synthesis pathway, resulted in increased sensitivity to colistin. Adenylosuccinate is subsequently converted to AMP, which is phosphorylated to produce ADP, a substrate for ATP synthesis. The amount of ATP was lower in the purA-knockout mutant than that in the wild-type strain. ATP synthesis is coupled with proton transfer, and it contributes to the membrane potential. Using the membrane potential probe, 3,3′-diethyloxacarbocyanine iodide [DiOC2(3)], we found that the membrane was hyperpolarized in the purA-knockout mutant compared to that in the wild-type strain. Treatment with the proton uncoupler, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), abolished the hyperpolarization and colistin sensitivity in the mutant. The purA-knockout mutant exhibited increased sensitivity to aminoglycosides, kanamycin, and gentamicin; their uptake requires a membrane potential. Therefore, the knockout of purA, an adenylosuccinate synthase, decreases ATP synthesis concurrently with membrane hyperpolarization, resulting in increased sensitivity to colistin. |
| 巻・号 | 371 |
| 公開日 | 2024-1-9 |
| DOI | 10.1093/femsle/fnae007 |
| PMID | 38305138 |
| PMC | PMC10876104 |
| MeSH | Adenosine Triphosphate Adenylosuccinate Synthase* Anti-Bacterial Agents / pharmacology Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology Colistin / pharmacology Escherichia coli* / genetics Microbial Sensitivity Tests Protons |
| IF | 1.987 |
| 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 | |
| 原核生物(大腸菌) | ME9062 JW4135-KC JW3606-KC |