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Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A
- Source :
- Angewandte Chemie (Int. ed., Print) 60 (2021): 10023–10031. doi:10.1002/anie.202012374, info:cnr-pdr/source/autori: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/titolo:Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A/doi:10.1002%2Fanie.202012374/rivista:Angewandte Chemie (Int. ed., Print)/anno:2021/pagina_da:10023/pagina_a:10031/intervallo_pagine:10023–10031/volume:60, Angewandte Chemie International Edition, Angewandte Chemie (International Ed. in English)
- Publication Year :
- 2021
- Publisher :
- Wiley-VCH., Weinheim, Germania, 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.<br />A host–microbe chemical ecology study revealed an effective and safe immunomodulator from Alcaligenes faecalis resident in gut‐associated lymphoid tissues, Peyer's patches (see picture). The complete structures of both the lipooligosaccharide and the lipopolysaccharide from A. faecalis were characterized. Furthermore, A. faecalis lipid A molecules were synthesized with varying degrees of acylation and found to be a promising vaccine adjuvant candidate.
- Subjects :
- glycolipids
Lipopolysaccharide
Gut-associated lymphoid tissue
01 natural sciences
Lipid A
Mice
chemistry.chemical_compound
Carbohydrate Conformation
Receptor
Research Articles
0303 health sciences
Alcaligenes faecalis
biology
lipopolysaccharide
General Medicine
vaccines
3. Good health
medicine.anatomical_structure
lipids (amino acids, peptides, and proteins)
Vaccine Adjuvants
Research Article
Agonist
medicine.drug_class
010402 general chemistry
Catalysis
Cell Line
Microbiology
03 medical and health sciences
Glycolipid
oligosaccharides
medicine
oligosaccharide
Animals
Humans
lipid A
030304 developmental biology
Interleukin-6
010405 organic chemistry
General Chemistry
biology.organism_classification
lipopolysaccharides
0104 chemical sciences
Toll-Like Receptor 4
lipid
chemistry
TLR4
glycolipid
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie (Int. ed., Print) 60 (2021): 10023–10031. doi:10.1002/anie.202012374, info:cnr-pdr/source/autori: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/titolo:Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A/doi:10.1002%2Fanie.202012374/rivista:Angewandte Chemie (Int. ed., Print)/anno:2021/pagina_da:10023/pagina_a:10031/intervallo_pagine:10023–10031/volume:60, Angewandte Chemie International Edition, Angewandte Chemie (International Ed. in English)
- Accession number :
- edsair.doi.dedup.....83cc032fb2183f8dfbb9f37acafa1ed9
- Full Text :
- https://doi.org/10.1002/anie.202012374