Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.18/6328 |
Resumo: | Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/ |
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Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranesAnti-Bacterial AgentsBacillus anthracisBacillus cereusCaco-2 CellsCarbohydrate ConformationCell MembraneCell SurvivalCell WallGlycosidesHumansKineticsLipid BilayersMicrobial Sensitivity TestsMicrobial ViabilityPhase TransitionPhosphatidylethanolaminesStructure-Activity RelationshipFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax 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.The 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.).Nature ResearchRepositório Científico do Instituto Nacional de SaúdeDias, CatarinaPais, João P.Nunes, RafaelBlázquez-Sánchez, Maria-TeresaMarquês, Joaquim T.Almeida, Andreia F.Serra, PatríciaXavier, Nuno M.Vila-Viçosa, DiogoMachuqueiro, MiguelViana, Ana S.Martins, AliceSantos, Maria S.Pelerito, AnaDias, RicardoTenreiro, RogérioOliveira, Maria C.Contino, MarialessandraColabufo, Nicola A.de Almeida, Rodrigo F.M.Rauter, Amélia P.2019-03-27T12:10:52Z2018-11-192018-11-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6328engNat Commun. 2018 Nov 19;9(1):4857. doi: 10.1038/s41467-018-06488-42041-172310.1038/s41467-018-06488-4info: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:RCAAP2023-07-20T15:41:21Zoai:repositorio.insa.pt:10400.18/6328Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:58.688238Repositório 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 |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| title |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| spellingShingle |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes Dias, Catarina Anti-Bacterial Agents Bacillus anthracis Bacillus cereus Caco-2 Cells Carbohydrate Conformation Cell Membrane Cell Survival Cell Wall Glycosides Humans Kinetics Lipid Bilayers Microbial Sensitivity Tests Microbial Viability Phase Transition Phosphatidylethanolamines Structure-Activity Relationship |
| title_short |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| title_full |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| title_fullStr |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| title_full_unstemmed |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| title_sort |
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes |
| author |
Dias, Catarina |
| author_facet |
Dias, Catarina Pais, João P. Nunes, Rafael Blázquez-Sánchez, Maria-Teresa Marquês, Joaquim T. Almeida, Andreia F. Serra, Patrícia Xavier, Nuno M. Vila-Viçosa, Diogo Machuqueiro, Miguel Viana, Ana S. Martins, Alice Santos, Maria S. Pelerito, Ana Dias, Ricardo Tenreiro, Rogério Oliveira, Maria C. Contino, Marialessandra Colabufo, Nicola A. de Almeida, Rodrigo F.M. Rauter, Amélia P. |
| author_role |
author |
| author2 |
Pais, João P. Nunes, Rafael Blázquez-Sánchez, Maria-Teresa Marquês, Joaquim T. Almeida, Andreia F. Serra, Patrícia Xavier, Nuno M. Vila-Viçosa, Diogo Machuqueiro, Miguel Viana, Ana S. Martins, Alice Santos, Maria S. Pelerito, Ana Dias, Ricardo Tenreiro, Rogério Oliveira, Maria C. Contino, Marialessandra Colabufo, Nicola A. de Almeida, Rodrigo F.M. Rauter, Amélia P. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
| dc.contributor.author.fl_str_mv |
Dias, Catarina Pais, João P. Nunes, Rafael Blázquez-Sánchez, Maria-Teresa Marquês, Joaquim T. Almeida, Andreia F. Serra, Patrícia Xavier, Nuno M. Vila-Viçosa, Diogo Machuqueiro, Miguel Viana, Ana S. Martins, Alice Santos, Maria S. Pelerito, Ana Dias, Ricardo Tenreiro, Rogério Oliveira, Maria C. Contino, Marialessandra Colabufo, Nicola A. de Almeida, Rodrigo F.M. Rauter, Amélia P. |
| dc.subject.por.fl_str_mv |
Anti-Bacterial Agents Bacillus anthracis Bacillus cereus Caco-2 Cells Carbohydrate Conformation Cell Membrane Cell Survival Cell Wall Glycosides Humans Kinetics Lipid Bilayers Microbial Sensitivity Tests Microbial Viability Phase Transition Phosphatidylethanolamines Structure-Activity Relationship |
| topic |
Anti-Bacterial Agents Bacillus anthracis Bacillus cereus Caco-2 Cells Carbohydrate Conformation Cell Membrane Cell Survival Cell Wall Glycosides Humans Kinetics Lipid Bilayers Microbial Sensitivity Tests Microbial Viability Phase Transition Phosphatidylethanolamines Structure-Activity Relationship |
| description |
Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/ |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-11-19 2018-11-19T00:00:00Z 2019-03-27T12:10:52Z |
| 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/10400.18/6328 |
| url |
http://hdl.handle.net/10400.18/6328 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Nat Commun. 2018 Nov 19;9(1):4857. doi: 10.1038/s41467-018-06488-4 2041-1723 10.1038/s41467-018-06488-4 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Nature Research |
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Nature Research |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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