Polysaccharide-Targeting Lipid Nanoparticles to Kill Gram-Negative Bacteria.
antibiotic resistance
bacteria
lipid nanoparticles
model membranes
neutron reflectometry
polysaccharide
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
05 Oct 2023
05 Oct 2023
Historique:
revised:
16
08
2023
received:
15
06
2023
medline:
6
10
2023
pubmed:
6
10
2023
entrez:
5
10
2023
Statut:
aheadofprint
Résumé
The rapid increase and spread of Gram-negative bacteria resistant to many or all existing treatments threaten a return to the preantibiotic era. The presence of bacterial polysaccharides that impede the penetration of many antimicrobials and protect them from the innate immune system contributes to resistance and pathogenicity. No currently approved antibiotics target the polysaccharide regions of microbes. Here, describe monolaurin-based niosomes, the first lipid nanoparticles that can eliminate bacterial polysaccharides from hypervirulent Klebsiella pneumoniae, are described. Their combination with polymyxin B shows no cytotoxicity in vitro and is highly effective in combating K. pneumoniae infection in vivo. Comprehensive mechanistic studies have revealed that antimicrobial activity proceeds via a multimodal mechanism. Initially, lipid nanoparticles disrupt polysaccharides, then outer and inner membranes are destabilized and destroyed by polymyxin B, resulting in synergistic cell lysis. This novel lipidic nanoparticle system shows tremendous promise as a highly effective antimicrobial treatment targeting multidrug-resistant Gram-negative pathogens.
Identifiants
pubmed: 37798622
doi: 10.1002/smll.202305052
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2305052Subventions
Organisme : National Health and Medical Research Council
ID : APP1144652
Organisme : National Health and Medical Research Council
ID : APP2002921
Informations de copyright
© 2023 The Authors. Small published by Wiley-VCH GmbH.
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