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- Title
Lipopolysaccharide from Gut‐Associated Lymphoid‐Tissue‐Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A.
- Authors
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
- Abstract
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.
- Subjects
CHEMICAL structure; LIPID synthesis; CHEMICAL synthesis; LYMPHOID tissue; TOLL-like receptors; MYELOID differentiation factor 88; LIPOXINS
- Publication
Angewandte Chemie, 2021, Vol 133, Issue 18, p10111
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202012374