Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Catarina Dias, João P. Pais, Rafael Nunes, Maria-Teresa Blázquez-Sánchez, Joaquim T. Marquês, Andreia F. Almeida, Patrícia Serra, Nuno M. Xavier, Diogo Vila-Viçosa, Miguel Machuqueiro, Ana S. Viana, Alice Martins, Maria S. Santos, Ana Pelerito, Ricardo Dias, Rogério Tenreiro, Maria C. Oliveira, Marialessandra Contino, Nicola A. Colabufo, Rodrigo F. M. Almeida and Amélia P. Rauter ()
Additional contact information
Catarina Dias: Universidade de Lisboa
João P. Pais: Universidade de Lisboa
Rafael Nunes: Universidade de Lisboa
Maria-Teresa Blázquez-Sánchez: Universidade de Lisboa
Joaquim T. Marquês: Universidade de Lisboa
Andreia F. Almeida: Universidade de Lisboa
Patrícia Serra: Universidade de Lisboa
Nuno M. Xavier: Universidade de Lisboa
Diogo Vila-Viçosa: Universidade de Lisboa
Miguel Machuqueiro: Universidade de Lisboa
Ana S. Viana: Universidade de Lisboa
Alice Martins: Universidade de Lisboa
Maria S. Santos: Universidade de Lisboa
Ana Pelerito: Instituto Nacional de Saúde Doutor Ricardo Jorge
Ricardo Dias: Universidade de Lisboa
Rogério Tenreiro: Universidade de Lisboa
Maria C. Oliveira: Universidade de Lisboa
Marialessandra Contino: Università degli Studi di Bari
Nicola A. Colabufo: Università degli Studi di Bari
Rodrigo F. M. Almeida: Universidade de Lisboa
Amélia P. Rauter: Universidade de Lisboa

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06488-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06488-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06488-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().