Granulibacter bethesdensis, a Pathogen from Patients with Chronic Granulomatous Disease, Produces a Penta-Acylated Hypostimulatory Glycero-d-talo-oct-2-ulosonic Acid–Lipid A Glycolipid (Ko-Lipid A)
| Autor: | David E. Greenberg, Lars J. Berg, Artur Muszyński, Arina Kozyr, Harry L. Malech, John I. Gallin, Christian Heiss, Parastoo Azadi, Kol A. Zarember, Russell W. Carlson, Joseph Shiloach, John Audley, Steven M. Holland |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide 030106 microbiology Antimicrobial peptides Article Catalysis Microbiology Inorganic Chemistry Lipid A Gram-negative pathogen immunodeficiency lcsh:Chemistry Gram-negative pathogen 03 medical and health sciences chemistry.chemical_compound Glycolipid Ulosonic acid Physical and Theoretical Chemistry Molecular Biology lipid A lcsh:QH301-705.5 Spectroscopy NADPH oxidase biology Organic Chemistry lipopolysaccharide General Medicine biology.organism_classification Enterobacteriaceae Computer Science Applications 030104 developmental biology chemistry lcsh:Biology (General) lcsh:QD1-999 biology.protein Granulibacter bethesdensis lipids (amino acids peptides and proteins) immunodeficiency |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 3303, p 3303 (2021) International Journal of Molecular Sciences Volume 22 Issue 7 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis (Gb) is hypostimulatory compared to Escherichia coli, i.e., cytokine production in human blood requires 10–100 times more G. bethesdensis CFU/mL than E. coli. To better understand the pathogenicity of G. bethesdensis, we isolated its lipopolysaccharide (GbLPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae, the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Manp-(1→4)-β-GlcpN3N-(1→6)-α-GlcpN-(1⇿1)-α-GlcpA tetra-saccharide substituted with five acyl chains: the amide-linked N-3′ 14:0(3-OH), N-2′ 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of GbLPS. In addition, the presence of Ko and only five acyl chains may explain the > 10-fold lower proinflammatory potency of GbKo–lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko–lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides. |
| Databáze: | OpenAIRE |
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