Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria

Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have d...

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Detalles Bibliográficos
Autores: Grau Campistany, Ariadna, Manresa Presas, Ma. Ángeles (María Ángeles), Pujol Cubells, Montserrat, Rabanal Anglada, Francesc, Cajal Visa, Yolanda
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/164094
Acceso en línea:https://hdl.handle.net/2445/164094
Access Level:acceso abierto
Palabra clave:Pèptids
Antibiòtics
Peptides
Antibiotics
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spelling Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteriaGrau Campistany, AriadnaManresa Presas, Ma. Ángeles (María Ángeles)Pujol Cubells, MontserratRabanal Anglada, FrancescCajal Visa, YolandaPèptidsAntibiòticsPeptidesAntibioticsResistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three lipopeptides induce membrane fusion and leakage from anionic vesicles, a process that is favored by the presence of POPE. The molecules bind to zwitterionic POPC vesicles, a model of the eukaryotic membrane, but in a different way, with lower affinity, less penetration into the bilayer and no fusion or permeabilization of the membrane. Results in model membranes are consistent with flow cytometry experiments in Escherichia coli and Staphylococcus aureus using a membrane potential sensitive dye (bis-oxonol) and a nucleic acid dye (propidium iodide), suggesting that the mechanism of action is based on membrane binding and collapse of membrane integrity by depolarization and permeabilization. (C) 2015 Elsevier B.V. All rights reserved.Elsevier B.V.2020202020162020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion27 p.application/pdfhttps://hdl.handle.net/2445/164094Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1016/j.bbamem.2015.11.011Biochimica et Biophysica Acta-Biomembranes, 2016, vol. 1858, num. 2, p. 333-343https://doi.org/10.1016/j.bbamem.2015.11.011cc-by-nc-nd (c) Elsevier B.V., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1640942026-05-29T05:05:01Z
dc.title.none.fl_str_mv Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
title Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
spellingShingle Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
Grau Campistany, Ariadna
Pèptids
Antibiòtics
Peptides
Antibiotics
title_short Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
title_full Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
title_fullStr Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
title_full_unstemmed Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
title_sort Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria
dc.creator.none.fl_str_mv Grau Campistany, Ariadna
Manresa Presas, Ma. Ángeles (María Ángeles)
Pujol Cubells, Montserrat
Rabanal Anglada, Francesc
Cajal Visa, Yolanda
author Grau Campistany, Ariadna
author_facet Grau Campistany, Ariadna
Manresa Presas, Ma. Ángeles (María Ángeles)
Pujol Cubells, Montserrat
Rabanal Anglada, Francesc
Cajal Visa, Yolanda
author_role author
author2 Manresa Presas, Ma. Ángeles (María Ángeles)
Pujol Cubells, Montserrat
Rabanal Anglada, Francesc
Cajal Visa, Yolanda
author2_role author
author
author
author
dc.subject.none.fl_str_mv Pèptids
Antibiòtics
Peptides
Antibiotics
topic Pèptids
Antibiòtics
Peptides
Antibiotics
description Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three lipopeptides induce membrane fusion and leakage from anionic vesicles, a process that is favored by the presence of POPE. The molecules bind to zwitterionic POPC vesicles, a model of the eukaryotic membrane, but in a different way, with lower affinity, less penetration into the bilayer and no fusion or permeabilization of the membrane. Results in model membranes are consistent with flow cytometry experiments in Escherichia coli and Staphylococcus aureus using a membrane potential sensitive dye (bis-oxonol) and a nucleic acid dye (propidium iodide), suggesting that the mechanism of action is based on membrane binding and collapse of membrane integrity by depolarization and permeabilization. (C) 2015 Elsevier B.V. All rights reserved.
publishDate 2016
dc.date.none.fl_str_mv 2016
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/164094
url https://hdl.handle.net/2445/164094
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.bbamem.2015.11.011
Biochimica et Biophysica Acta-Biomembranes, 2016, vol. 1858, num. 2, p. 333-343
https://doi.org/10.1016/j.bbamem.2015.11.011
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier B.V., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier B.V., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 27 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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