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Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives

[Image: see text] Antimicrobial peptides that act by disrupting bacterial membranes are attractive agents for treating drug-resistant bacteria. This study investigates a membrane-disrupting peptide mimic made of a cyclic oligosaccharide cyclodextrin scaffold that can be chemically polyfunctionalized...

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Autores principales: Yamamura, Hatsuo, Hagiwara, Tatsuya, Hayashi, Yuma, Osawa, Kayo, Kato, Hisato, Katsu, Takashi, Masuda, Kazufumi, Sumino, Ayumi, Yamashita, Hayato, Jinno, Ryo, Abe, Masayuki, Miyagawa, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638021/
https://www.ncbi.nlm.nih.gov/pubmed/34870006
http://dx.doi.org/10.1021/acsomega.1c04541
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author Yamamura, Hatsuo
Hagiwara, Tatsuya
Hayashi, Yuma
Osawa, Kayo
Kato, Hisato
Katsu, Takashi
Masuda, Kazufumi
Sumino, Ayumi
Yamashita, Hayato
Jinno, Ryo
Abe, Masayuki
Miyagawa, Atsushi
author_facet Yamamura, Hatsuo
Hagiwara, Tatsuya
Hayashi, Yuma
Osawa, Kayo
Kato, Hisato
Katsu, Takashi
Masuda, Kazufumi
Sumino, Ayumi
Yamashita, Hayato
Jinno, Ryo
Abe, Masayuki
Miyagawa, Atsushi
author_sort Yamamura, Hatsuo
collection PubMed
description [Image: see text] Antimicrobial peptides that act by disrupting bacterial membranes are attractive agents for treating drug-resistant bacteria. This study investigates a membrane-disrupting peptide mimic made of a cyclic oligosaccharide cyclodextrin scaffold that can be chemically polyfunctionalized. An antibacterial functional group on the peptide was simplified to an alkylamino group that combines cationic and hydrophobic moieties, the former to interact with the anionic bacterial membrane and the latter with the membrane interior. The cyclodextrins equipped with eight alkylamino groups on the molecules using a poly-click reaction exhibited antibacterial activity against Gram-positive and Gram-negative bacteria, including drug-resistant pathogens such as carbapenem-resistant Enterobacteriaceae. Several lines of evidence showed that these agents disrupt bacterial membranes, leading to rapid bacterial cell death. The resulting membrane perturbation was directly visualized using high-speed atomic force microscopy imaging. In Gram-negative bacteria, the membrane-permeabilizing action of these derivatives allowed the entry of co-treated traditional antibiotics, which were then active against these bacteria.
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spelling pubmed-86380212021-12-03 Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives Yamamura, Hatsuo Hagiwara, Tatsuya Hayashi, Yuma Osawa, Kayo Kato, Hisato Katsu, Takashi Masuda, Kazufumi Sumino, Ayumi Yamashita, Hayato Jinno, Ryo Abe, Masayuki Miyagawa, Atsushi ACS Omega [Image: see text] Antimicrobial peptides that act by disrupting bacterial membranes are attractive agents for treating drug-resistant bacteria. This study investigates a membrane-disrupting peptide mimic made of a cyclic oligosaccharide cyclodextrin scaffold that can be chemically polyfunctionalized. An antibacterial functional group on the peptide was simplified to an alkylamino group that combines cationic and hydrophobic moieties, the former to interact with the anionic bacterial membrane and the latter with the membrane interior. The cyclodextrins equipped with eight alkylamino groups on the molecules using a poly-click reaction exhibited antibacterial activity against Gram-positive and Gram-negative bacteria, including drug-resistant pathogens such as carbapenem-resistant Enterobacteriaceae. Several lines of evidence showed that these agents disrupt bacterial membranes, leading to rapid bacterial cell death. The resulting membrane perturbation was directly visualized using high-speed atomic force microscopy imaging. In Gram-negative bacteria, the membrane-permeabilizing action of these derivatives allowed the entry of co-treated traditional antibiotics, which were then active against these bacteria. American Chemical Society 2021-11-15 /pmc/articles/PMC8638021/ /pubmed/34870006 http://dx.doi.org/10.1021/acsomega.1c04541 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Yamamura, Hatsuo
Hagiwara, Tatsuya
Hayashi, Yuma
Osawa, Kayo
Kato, Hisato
Katsu, Takashi
Masuda, Kazufumi
Sumino, Ayumi
Yamashita, Hayato
Jinno, Ryo
Abe, Masayuki
Miyagawa, Atsushi
Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title_full Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title_fullStr Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title_full_unstemmed Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title_short Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives
title_sort antibacterial activity of membrane-permeabilizing bactericidal cyclodextrin derivatives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638021/
https://www.ncbi.nlm.nih.gov/pubmed/34870006
http://dx.doi.org/10.1021/acsomega.1c04541
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