Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems

Detalhes bibliográficos
Autor(a) principal: Domingues, Marco M.
Data de Publicação: 2012
Outros Autores: Inácio, Rita G., Raimundo, José M., Martins, Miguel, Castanho, Miguel A. R. B., Santos, Nuno C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/10757
Resumo: © 2012 Wiley Periodicals, Inc.
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spelling Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systemsPolymyxin BLipopolysaccharideMembrane model systems© 2012 Wiley Periodicals, Inc.Antibiotic resistance is an increasingly severe health problem. Antimicrobial peptides (AMPs) are being developed in order to overcome this problem, due to their lower bacterial resistance. Polymyxin B is an AMP with bactericidal effect on Gram-negative bacteria due to its high affinity for lipopolysaccharide (LPS). The objective of this work was to unravel the polymyxin B mechanisms of LPS neutralization and bactericidal activity. Using dynamic light scattering, it was observed that polymyxin B induces LPS aggregation in a concentration-dependent manner. The peptide increases the surface charge of LPS and membrane model systems, as revealed by zetapotential measurements. The higher zeta-potential variations were detected in the presence of the negatively charged POPG membranes. This higher interaction with negatively charged membranes, made of POPG, was followed at higher peptide concentration by membrane permeabilization. Also, for zwitterionic POPC membranes a higher membrane leakage was detected. The peptide promotion of LPS aggregation may be related with the clearance of LPS from the bloodstream, eventually by facilitating macrophage phagocytosis and/or blocking the binding of LPS to its receptor. Our data indicate that polymyxin B mechanism of action at the molecular level involves a first step of electrostatic approach toward LPS; then, it may be internalized and bind to the bacterial phosphatidylglycerol-rich membrane leaflets, inducing leakage at higher peptide concentrations.Contract grant sponsor: Fundação para a Ciência e a Tecnologia – Ministério do Ensino e Ciência (FCT-MES, Portugal). Contract grant number: PTDC/SAU-BEB/099142/2008. Contract grant sponsors: Gabinete de Apoio à Investigação Científica, Tecnológica e Inovação (GAPIC), of the Faculdade de Medicina da Universidade de Lisboa. Contract grant sponsor: FCT-MÊS. Contract grant number: SFRH/BD/41750/2007.WileyRepositório da Universidade de LisboaDomingues, Marco M.Inácio, Rita G.Raimundo, José M.Martins, MiguelCastanho, Miguel A. R. B.Santos, Nuno C.2014-03-21T10:17:24Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/10757engPeptideScience, Volume 98 / Number 40006-3525http://dx.doi.org/10.1002/bip.22095metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:56:28Zoai:repositorio.ul.pt:10451/10757Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:34:40.887100Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
title Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
spellingShingle Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
Domingues, Marco M.
Polymyxin B
Lipopolysaccharide
Membrane model systems
title_short Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
title_full Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
title_fullStr Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
title_full_unstemmed Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
title_sort Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems
author Domingues, Marco M.
author_facet Domingues, Marco M.
Inácio, Rita G.
Raimundo, José M.
Martins, Miguel
Castanho, Miguel A. R. B.
Santos, Nuno C.
author_role author
author2 Inácio, Rita G.
Raimundo, José M.
Martins, Miguel
Castanho, Miguel A. R. B.
Santos, Nuno C.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Domingues, Marco M.
Inácio, Rita G.
Raimundo, José M.
Martins, Miguel
Castanho, Miguel A. R. B.
Santos, Nuno C.
dc.subject.por.fl_str_mv Polymyxin B
Lipopolysaccharide
Membrane model systems
topic Polymyxin B
Lipopolysaccharide
Membrane model systems
description © 2012 Wiley Periodicals, Inc.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-01-01T00:00:00Z
2014-03-21T10:17:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/10757
url http://hdl.handle.net/10451/10757
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PeptideScience, Volume 98 / Number 4
0006-3525
http://dx.doi.org/10.1002/bip.22095
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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