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Korneev KV, Kondakova AN, Sviriaeva EN, Mitkin NA, Palmigiano A, Kruglov AA, Telegin GB, Drutskaya MS, Sturiale L, Garozzo D, Nedospasov SA, Knirel YA, Kuprash DV
Hypoacylated LPS from foodborne pathogen Campylobacter jejuni induces moderate TLR4-mediated inflammatory response in murine macrophages
Frontiers in Cellular and Infection Microbiology 8 (2018)
3HOMyr-(1-3)-+
|
?%EtN-(1--P--1)--+ |
| |
Pam-(1-3)-3HOMyr-(1-3)-+ | |
| | |
Pam-(1-3)-3HOMyr-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN
| |
P-4)-+ 3HOMyr-(1-2)-+ |
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Campylobacter jejuni O2A
(Ancestor NCBI TaxID 197,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Campylobacter jejuni [ICD11:
XN4Q5 
]
The structure was elucidated in this paperNCBI PubMed ID: 29535976Publication DOI: 10.3389/fcimb.2018.00058Journal NLM ID: 101585359Publisher: Lausanne: Frontiers Media SA
Correspondence: Dmitry V. Kuprash <kuprash

gmail.com>
Institutions: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia, CNR Institute for Polymers Composites and Biomaterials, Catania, Italy, Department of Immunology, Biological Faculty, Lomonosov Moscow State University, Moscow, Russia, German Rheumatism Research Center, Leibniz Institute, Berlin, Germany, Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia
Toll-like receptor 4 (TLR4) initiates immune response against Gram-negative bacteria upon specific recognition of lipid A moiety of lipopolysaccharide (LPS), the major component of their cell wall. Some natural differences between LPS variants in their ability to interact with TLR4 may lead to either insufficient activation that may not prevent bacterial growth, or excessive activation which may lead to septic shock. In this study we evaluated the biological activity of LPS isolated from pathogenic strain of Campylobacter jejuni, the most widespread bacterial cause of foodborne diarrhea in humans. With the help of hydrophobic chromatography and MALDI-TOF mass spectrometry we showed that LPS from a C. jejuni strain O2A consists of both hexaacyl and tetraacyl forms. Since such hypoacylation can result in a reduced immune response in humans, we assessed the activity of LPS from C. jejuni in mouse macrophages by measuring its capacity to activate TLR4-mediated proinflammatory cytokine and chemokine production, as well as NF?B-dependent reporter gene transcription. Our data support the hypothesis that LPS acylation correlates with its bioactivity.
LPS, lipid A, Campylobacter jejuni, pathogenic bacteria, macrophages, TLR4, acyl chains, proinflammatory cytokines
Structure type: oligomer ; 2002.2
Location inside paper: fig.1, hexaacyl lipid A
Compound class: lipid A
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_137340,IEDB_141181,IEDB_141807,IEDB_151531
Methods: ELISA, MALDI-TOF MS, biological assays, cytokine analysis, RT-PCR, statistical analysis, LPS bioactivity in murine macrophages
Biological activity: a higher acylated lipid A moiety are better inducers of TLR4-signaling
Related record ID(s): 12931
NCBI Taxonomy refs (TaxIDs): 197
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Korneev KV, Kondakova AN, Sviriaeva EN, Mitkin NA, Palmigiano A, Kruglov AA, Telegin GB, Drutskaya MS, Sturiale L, Garozzo D, Nedospasov SA, Knirel YA, Kuprash DV
Hypoacylated LPS from foodborne pathogen Campylobacter jejuni induces moderate TLR4-mediated inflammatory response in murine macrophages
Frontiers in Cellular and Infection Microbiology 8 (2018)
3HOMyr-(1-3)-+ 3HOMyr-(1-2)-+
| |
3HOMyr-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
P-4)-+ 3HOMyr-(1-3)-+ |
Show graphically |
Campylobacter jejuni O2A
(Ancestor NCBI TaxID 197,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Campylobacter jejuni [ICD11:
XN4Q5 
]
The structure was elucidated in this paperNCBI PubMed ID: 29535976Publication DOI: 10.3389/fcimb.2018.00058Journal NLM ID: 101585359Publisher: Lausanne: Frontiers Media SA
Correspondence: Dmitry V. Kuprash <kuprash

gmail.com>
Institutions: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia, CNR Institute for Polymers Composites and Biomaterials, Catania, Italy, Department of Immunology, Biological Faculty, Lomonosov Moscow State University, Moscow, Russia, German Rheumatism Research Center, Leibniz Institute, Berlin, Germany, Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia
Toll-like receptor 4 (TLR4) initiates immune response against Gram-negative bacteria upon specific recognition of lipid A moiety of lipopolysaccharide (LPS), the major component of their cell wall. Some natural differences between LPS variants in their ability to interact with TLR4 may lead to either insufficient activation that may not prevent bacterial growth, or excessive activation which may lead to septic shock. In this study we evaluated the biological activity of LPS isolated from pathogenic strain of Campylobacter jejuni, the most widespread bacterial cause of foodborne diarrhea in humans. With the help of hydrophobic chromatography and MALDI-TOF mass spectrometry we showed that LPS from a C. jejuni strain O2A consists of both hexaacyl and tetraacyl forms. Since such hypoacylation can result in a reduced immune response in humans, we assessed the activity of LPS from C. jejuni in mouse macrophages by measuring its capacity to activate TLR4-mediated proinflammatory cytokine and chemokine production, as well as NF?B-dependent reporter gene transcription. Our data support the hypothesis that LPS acylation correlates with its bioactivity.
LPS, lipid A, Campylobacter jejuni, pathogenic bacteria, macrophages, TLR4, acyl chains, proinflammatory cytokines
Structure type: oligomer ; 1402.8
Location inside paper: fig.1, tetraacyl lipid A
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_137340,IEDB_141807,IEDB_151531
Methods: ELISA, MALDI-TOF MS, biological assays, cytokine analysis, RT-PCR, statistical analysis, LPS bioactivity in murine macrophages
Related record ID(s): 12646
NCBI Taxonomy refs (TaxIDs): 197
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Richardson MB, Torigoe S, Yamasaki S, Williams SJ
Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships
Chemical Communications 51(81) (2015)
15027-15030
Mycobacterium tuberculosis H37Ra
(NCBI TaxID 419947,
species name lookup)
Taxonomic group: bacteria / Actinobacteria
(Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium tuberculosis [ICD11:
XN1N2 
]
NCBI PubMed ID: 26310657Publication DOI: 10.1039/c5cc04773kJournal NLM ID: 9610838Publisher: Cambridge: Royal Society of Chemistry
Correspondence: Williams SJ <sjwill

unimelb.edu.au>; Yamasaki S <yamasaki

bioreg.kyushu-u.ac.jp>
Institutions: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia, Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
Mycobacterium tuberculosis H37Ra produces a range of immunogenic β-gentiobiosyl diacylglycerides. We report the total synthesis of several candidate structures and show that these compounds signal weakly through mouse, but not human, Mincle. Structure-activity relationships reveal a striking dependence upon acyl chain length for gentiobiosyl diacylglyceride signalling through Mincle. Significantly, a truncated β-glucosyl diglyceride was shown to provide potent signalling through both human and mouse Mincle and could activate murine bone marrow derived dendritic cells
synthesis, Mycobacterium tuberculosis, β-gentiobiosyl diacylglycerides, Mincle receptor
Structure type: oligomer
Location inside paper: Fig. 1
Compound class: glycoglycerolipid, disaccharide
Contained glycoepitopes: IEDB_141806,IEDB_142488,IEDB_146664,IEDB_241101,IEDB_983931,SB_192
Methods: chemical synthesis, biological assays, cytokines tumor necrosis factor alpha (TNF-a) assay, determination of NO production, LPS bioactivity in murine macrophages
Biological activity: compound demonstrated direct binding to mouse Mincle and the ability to stimulate cytokine production by murine BMDCs only in the case of LIP = C12 (lauric acid)
Synthetic data: chemical
NCBI Taxonomy refs (TaxIDs): 419947
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