BIBLIOS

Tipo
Artigos em Revista

Tipo de Documento
Artigo Completo

Título
Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Participantes na publicação
Catarina Dias (Author)
João P. Pais (Author)
Rafael Nunes (Author)
BioISI
CQB
Maria-Teresa Blázquez-Sánchez (Author)
CQB
CQE
Joaquim T. Marquês (Author)
Dep. Química e Bioquímica
CQE
Andreia F. Almeida (Author)
Patrícia Serra (Author)
CQB
Nuno M. Xavier (Author)
CQB
CQE
Diogo Vila-Viçosa (Author)
CQB
BioISI
Miguel Machuqueiro (Author)
Dep. Química e Bioquímica
CQB
BioISI
Ana S. Viana (Author)
Dep. Química e Bioquímica
Dep. Química e Bioquímica
CQE
Alice Martins (Author)
CQB
Maria S. Santos (Author)
Dep. Química e Bioquímica
CQB
Ana Pelerito (Author)
Ricardo Dias (Author)
Rogério Tenreiro (Author)
Dep. Biologia Vegetal
BioISI
Maria C. Oliveira (Author)
Marialessandra Contino (Author)
Nicola A. Colabufo (Author)
Rodrigo F. M. de Almeida (Author)
CQB
CQE
Amélia P. Rauter (Author)
Dep. Química e Bioquímica
CQB

Resumo
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.


Instituição
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Suporte
Nature Communications

Identificadores da Publicação
ISSN - 2041-1723

Editora
Springer Nature



Identificadores do Documento
URL - http://dx.doi.org/10.1038/s41467-018-06488-4
DOI - https://doi.org/10.1038/s41467-018-06488-4

Distinções
Nature Communications Top 2% Chemistry Miscellaneous

Identificadores de Qualidade
Web Of Science Q1 (2018) - 11.878 - Multidisciplinary Sciences
SCIMAGO Q1 (2018) - 5.992 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
SCIMAGO Q1 (2018) - 5.992 - Chemistry (miscellaneous)
SCIMAGO Q1 (2018) - 5.992 - Physics and Astronomy (miscellaneous)

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