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.

Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A / Shimoyama, A.; Di Lorenzo, F.; Yamaura, H.; Mizote, K.; Palmigiano, A.; Pither, M. D.; Speciale, I.; Uto, T.; Masui, S.; Sturiale, L.; Garozzo, D.; Hosomi, K.; Shibata, N.; Kabayama, K.; Fujimoto, Y.; Silipo, A.; Kunisawa, J.; Kiyono, H.; Molinaro, A.; Fukase, K.. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 60:18(2021), pp. 10023-10031. [10.1002/anie.202012374]

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

Di Lorenzo F.;Pither M. D.;Speciale I.;Silipo A.;Molinaro A.;Fukase K.
2021

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.
2021
Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A / Shimoyama, A.; Di Lorenzo, F.; Yamaura, H.; Mizote, K.; Palmigiano, A.; Pither, M. D.; Speciale, I.; Uto, T.; Masui, S.; Sturiale, L.; Garozzo, D.; Hosomi, K.; Shibata, N.; Kabayama, K.; Fujimoto, Y.; Silipo, A.; Kunisawa, J.; Kiyono, H.; Molinaro, A.; Fukase, K.. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 60:18(2021), pp. 10023-10031. [10.1002/anie.202012374]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/853764
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