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rBPI(21) promotes lipopolysaccharide aggregation and exerts its antimicrobial effects by (hemi)fusion of PG-containing membranes

2009-12-22Artigo científico Acesso aberto
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dc.contributor.authorDomingues, Marco
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorSantos, Nuno C.
dc.date.accessioned2021-05-31T15:21:27Z
dc.date.available2021-05-31T15:21:27Z
dc.date.issued2009-12-22
dc.description© 2009 Domingues et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.pt_PT
dc.description.abstractAntimicrobial peptides (AMPs) are important potential alternatives to conventional therapies against bacterial infections. rBPI(21) is a 21 kDa peptide based on the N-terminal region of the neutrophil bactericidal/permeability-increasing protein (BPI). This AMP possesses highly selective bactericidal effects on Gram-negative bacteria and have affinity for lipopolysaccharide (LPS) which is believed to be at the origin of its neutralizing effect of the LPS segregated into the bloodstream. We aim at understanding the molecular bases of rBPI(21) bactericidal and LPS neutralization actions, using biomembrane model systems. Using dynamic light scattering spectroscopy we demonstrate that rBPI(21) promotes aggregation of negatively charged large unilamellar vesicles (LUV), even in the absence of LPS, and LPS aggregates, while for zwitterionic phosphatidylcholine (POPC) LUV the size remains unchanged. The peptide also promotes the fusion (or hemifusion) of membranes containing phosphatidylglycerol (POPG). The aggregation and fusion of negatively charged LUV are peptide concentration-dependent until massive aggregation is reached, followed by sample flocculation/precipitation. Concomitantly, there is a progressive change in the zeta-potential of the LUV systems and LPS aggregates. LUV systems composed of phosphatidylglycerol (POPG) and lipid mixtures with POPG have higher zeta-potential variations than in the absence of POPG. The interaction of rBPI(21) with lipid vesicles is followed by leakage, with higher effect in POPG-containing membranes. LPS aggregation can be related with a decreased toxicity, possibly by facilitating its clearance by macrophage phagocytosis and/or blocking of LPS specific receptor recognition. Our data indicate that rBPI(21) mechanism of action at the molecular level involves the interaction with the LPS of the outer membrane of Gram-negative bacteria, followed by internalization and leakage induction through the (hemi)fusion of the bacterial outer and inner membranes, both enriched in phosphatidylglycerol.pt_PT
dc.description.sponsorshipThis work was partially supported by Fundação para a Ciência e a Tecnologia (FCT), from the Ministério da Ciência, Tecnologia e Ensino Superior (Portugal). M.M.D. acknowledges FCT PhD fellowship SFRH/BD/41750/2007.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPLoS One. 2009 Dec 22;4(12):e8385.pt_PT
dc.identifier.doi10.1371/journal.pone.0008385pt_PT
dc.identifier.eissn1932-6203
dc.identifier.urihttp://hdl.handle.net/10451/48269
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttps://journals.plos.org/plosone/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titlerBPI(21) promotes lipopolysaccharide aggregation and exerts its antimicrobial effects by (hemi)fusion of PG-containing membranespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BD/41750/2007
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F41750%2F2007/PT
oaire.citation.issue12pt_PT
oaire.citation.startPagee8385pt_PT
oaire.citation.titlePloS Onept_PT
oaire.citation.volume4pt_PT
oaire.fundingStreamSFRH
person.familyNameDomingues
person.familyNameCastanho
person.familyNameSantos
person.givenNameMarco
person.givenNameMiguel
person.givenNameNuno
person.identifier.ciencia-idE317-92F8-84C6
person.identifier.ciencia-idCD13-5E3A-A3C5
person.identifier.orcid0000-0003-1502-1421
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-0580-0475
person.identifier.ridN-7248-2013
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id55940818300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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