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Lipopolysaccharide from Gut‐Associated Lymphoid‐Tissue‐Resident Alcaligenes faecalis : Complete Structure Determination and Chemical Synthesis of Its Lipid A
Author(s) -
Shimoyama Atsushi,
Di Lorenzo Flaviana,
Yamaura Haruki,
Mizote Keisuke,
Palmigiano Angelo,
Pither Molly D.,
Speciale Immacolata,
Uto Tomoya,
Masui Seiji,
Sturiale Luisa,
Garozzo Domenico,
Hosomi Koji,
Shibata Naoko,
Kabayama Kazuya,
Fujimoto Yukari,
Silipo Alba,
Kunisawa Jun,
Kiyono Hiroshi,
Molinaro Antonio,
Fukase Koichi
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202012374
Subject(s) - lipid a , lipopolysaccharide , alcaligenes faecalis , tlr4 , microbiology and biotechnology , chemistry , enterococcus faecalis , adjuvant , receptor , bacteria , biology , biochemistry , immunology , escherichia coli , gene , genetics
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.