Repository logo
 
Publication

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

2018-11-19Journal article Open access
Simple item page
dc.contributor.authorDias, Catarina
dc.contributor.authorPais, João P.
dc.contributor.authorNunes, Rafael
dc.contributor.authorBlázquez-Sánchez, Maria-Teresa
dc.contributor.authorMarquês, Joaquim T.
dc.contributor.authorAlmeida, Andreia F.
dc.contributor.authorSerra, Patrícia
dc.contributor.authorXavier, Nuno M.
dc.contributor.authorVila-Viçosa, Diogo
dc.contributor.authorMachuqueiro, Miguel
dc.contributor.authorViana, Ana S.
dc.contributor.authorMartins, Alice
dc.contributor.authorSantos, Maria S.
dc.contributor.authorPelerito, Ana
dc.contributor.authorDias, Ricardo
dc.contributor.authorTenreiro, Rogério
dc.contributor.authorOliveira, Maria C.
dc.contributor.authorContino, Marialessandra
dc.contributor.authorColabufo, Nicola A.
dc.contributor.authorde Almeida, Rodrigo F.M.
dc.contributor.authorRauter, Amélia P.
dc.date.accessioned2019-03-27T12:10:52Z
dc.date.available2019-03-27T12:10:52Z
dc.date.issued2018-11-19
dc.descriptionFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/pt_PT
dc.description.abstractAnthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.pt_PT
dc.description.sponsorshipThe European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2018 Nov 19;9(1):4857. doi: 10.1038/s41467-018-06488-4pt_PT
dc.identifier.doi10.1038/s41467-018-06488-4pt_PT
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10400.18/6328
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Researchpt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-018-06488-4pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAnti-Bacterial Agentspt_PT
dc.subjectBacillus anthracispt_PT
dc.subjectBacillus cereuspt_PT
dc.subjectCaco-2 Cellspt_PT
dc.subjectCarbohydrate Conformationpt_PT
dc.subjectCell Membranept_PT
dc.subjectCell Survivalpt_PT
dc.subjectCell Wallpt_PT
dc.subjectGlycosidespt_PT
dc.subjectHumanspt_PT
dc.subjectKineticspt_PT
dc.subjectLipid Bilayerspt_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectMicrobial Viabilitypt_PT
dc.subjectPhase Transitionpt_PT
dc.subjectPhosphatidylethanolaminespt_PT
dc.subjectStructure-Activity Relationshippt_PT
dc.titleSugar-based bactericides targeting phosphatidylethanolamine-enriched membranespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00612%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F42567%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBDE%2F51998%2F2012/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage4857pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStreamSFRH
oaire.fundingStreamSFRH
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctPolítica editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationd62aec29-d1a4-4269-a664-f807f4929dc5
relation.isProjectOfPublicationdc84f768-e6f2-4eea-b294-6c8ebbd1a156
relation.isProjectOfPublicationc9ebbb41-e49e-44d6-b193-f87732eff36c
relation.isProjectOfPublication4ac5a0ec-efb8-4a9e-a311-9e21b0246e67
relation.isProjectOfPublication.latestForDiscoverydc84f768-e6f2-4eea-b294-6c8ebbd1a156

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
21-Sugar-based bactericides targeting.pdf
Size:
3.04 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DDI - Artigos em revistas internacionais