期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 66, 期 23, 页码 3821-3826出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0129-9
关键词
Bacterial membrane; Cationic peptide antibiotics; Drug target; Gramicidin S; Polymyxin; Respiratory enzymes
资金
- Japan Society for the Promotion of Science [20570124, 18GS0314]
- Ministry of Education, Culture, Sports, Science and Technology, Japan. [18073004]
- Grants-in-Aid for Scientific Research [20570124] Funding Source: KAKEN
Gramicidin S and polymyxins are small cationic cyclic peptides and act as potent antibiotics against Gram-negative and Gram-positive bacteria by perturbing integrity of the bacterial membranes. Screening of a natural antibiotics library with bacterial membrane vesicles identified gramicidin S as an inhibitor of cytochrome bd quinol oxidase and an alternative NADH dehydrogenase (NDH-2) and polymyxin B as an inhibitor of NDH-2 and malate: quinone oxidoreductase. Our studies showed that cationic cyclic peptide antibiotics have novel molecular targets in the membrane and interfere ligand binding on the hydrophobic surface of enzymes. Improvement of the toxicity and optimization of the structures and clinical uses are urgently needed for their effective application in combating drug-resistant bacteria.
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