Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A.
glycolipids
lipid A
lipopolysaccharides
oligosaccharides
vaccines
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
26 04 2021
26 04 2021
Historique:
received:
10
09
2020
pubmed:
2
2
2021
medline:
7
8
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
Alcaligenes faecalis is the predominant Gram-negative bacterium inhabiting gut-associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1- and 4'-phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit a discrete interleukin-6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate.
Identifiants
pubmed: 33522128
doi: 10.1002/anie.202012374
pmc: PMC8252424
doi:
Substances chimiques
Interleukin-6
0
Lipid A
0
Lipopolysaccharides
0
TLR4 protein, human
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10023-10031Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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