Lipopolysaccharide from Gut-Associated Lymphoid Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of its Lipid As.

Alcaligenes faecalis is the predominant Gram-negative bacterium inhabiting gut-associated lymphoid tissues, Peyer's patches. We previously reported about A. faecalis lipopolysaccharide (LPS) acting as a weak agonist for Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) receptor while playing as a potent inducer of IgA without excessive inflammation. This suggests that A. faecalis LPS might be used as a safe adjuvant and boosted interest in the establishment of its chemical structure. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis . We synthesized three lipid As with a different acylation degree by an efficient route where 1- and 4'-phosphates were simultaneously introduced. The immunological characterization of the lipid As revealed that hexa-acylated A. faecalis lipid A has a moderate agonistic activity towards TLR4-mediated signaling and the capability to elicit a discrete interleukin (IL)-6 release in human cell lines and mice. Hexa-acylated A. faecalis lipid A was thus found to be the active principle of its LOS/LPS and a promising vaccine adjuvant candidate.