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

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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.

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Acknowledgments

We would like to thank anonymous referees for their expert comments. This work was supported by grant-in-aid for Scientific Research (C) (20570124) and Creative Scientific Research (18GS0314) from the Japan Society for the Promotion of Science, and grant-in-aid for Scientific Research on Priority Areas (18073004) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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  1. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Tatsushi Mogi & Kiyoshi Kita

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  1. Tatsushi Mogi
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  2. Kiyoshi Kita
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Correspondence to Tatsushi Mogi or Kiyoshi Kita.

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Mogi, T., Kita, K. Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics. Cell. Mol. Life Sci. 66, 3821–3826 (2009). https://doi.org/10.1007/s00018-009-0129-9

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  • DOI: https://doi.org/10.1007/s00018-009-0129-9

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