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Cell Mol Life Sci. 2009 Dec;66(23):3821-6. doi: 10.1007/s00018-009-0129-9. Epub 2009 Aug 23.

Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics.

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1
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. tmogi@m.u-tokyo.ac.jp

Abstract

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.

PMID:
19701717
DOI:
10.1007/s00018-009-0129-9
[Indexed for MEDLINE]
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