Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A

Atsushi Shimoyama, Flaviana Di Lorenzo, Haruki Yamaura, Keisuke Mizote, Angelo Palmigiano, Molly D. Pither, Immacolata Speciale, Tomoya Uto, Seiji Masui, Luisa Sturiale, Domenico Garozzo, Koji Hosomi, Naoko Shibata, Kazuya Kabayama, Yukari Fujimoto, Alba Silipo, Jun Kunisawa, Hiroshi Kiyono, Antonio Molinaro, Koichi Fukase

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalAngewandte Chemie - International Edition
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • glycolipids
  • lipid A
  • lipopolysaccharides
  • oligosaccharides
  • vaccines

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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