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1. (Article ID: 496)
 
Trent MS
Biosynthesis, transport, and modification of lipid A
Biochemistry and Cell Biology 82(1) (2004) 71-86
 

Lipopolysaccharide (LPS) is the major surface molecule of Gram-negative bacteria and consists of three distinct structural domains: O-antigen, core, and lipid A. The lipid A (endotoxin) domain of LPS is a unique, glucosamine-based phospholipid that serves as the hydrophobic anchor of LPS and is the bioactive component of the molecule that is associated with Gram-negative septic shock. The structural genes encoding the enzymes required for the biosynthesis of Escherchia coli lipid A have been identified and characterized. Lipid A is often viewed as a constitutively synthesized structural molecule. However, determination of the exact chemical structures of lipid A from diverse Gram-negative bacteria shows that the molecule can be further modified in response to environmental stimuli. These modifications have been implicated in virulence of pathogenic Gram-negative bacteria and represent one of the molecular mechanisms of microbial surface remodeling used by bacteria to help evade the innate immune response. The intent of this review is to discuss the enzymatic machinery involved in the biosynthesis of lipid A, transport of the molecule, and finally, those enzymes involved in the modification of its structure in response to environmental stimuli.

lipopolysaccharides, lipide A, endotoxine, membrane externe, MsbA

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2. (Article ID: 565)
 
Kawasaki K, Ernst RK, Miller SI
3-O-Deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4
Journal of Biological Chemistry 279(19) (2004) 20044-20048
 

Toll-like receptor 4 (TLR4)-mediated responses, which are induced by the lipid A portion of lipopolysaccharide, are important for host defense against Salmonellae infection. A variety of different data indicate that the acylation state of lipid A can alter TLR4-mediated responses. The S. typhimurium virulence gene product PhoP/PhoQ signals the presence of host microenvironments to regulate the expression of a lipid A 3-O-deacylase, PagL, and a lipid A palmitoyltransferase, PagP. We now demonstrate that 3-O-deacylation and palmitoylation of lipid A decreases its ability to induce TLR4-mediated signaling. Deacylated lipid A, deacylated and palmitoylated lipid A, palmitoylated lipid A, and unmodified lipid A species were purified from Escherichia coli heterologously expressing PagL and/or PagP. The purified lipid A preparations showed spectra of a single lipid A species on mass spectrometry and gave a single band on thin layer chromatography. The activity of purified lipid A species was examined using human and mouse cell lines that express recombinant human TLR4. Compared with unmodified lipid A, the modified lipid A species are 30-100-fold less active in the ability to induce NF-kappaB-dependent reporter activation. These results suggest that the lipid A modifications reduce TLR4-signaling as part of Salmonellae adaptation to host environments.

Lipopolysaccharide, Escherichia coli, lipid A, mass spectrometrySalmonella typhimurium

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3. (Article ID: 8640)
 
Ma XK, Guo DD, Peterson EC, Dun Y, Li DY
Structural characterization and anti-aging activity of a novel extracellular polysaccharide from fungus Phellinus sp. in mammalian system
Food and Function 7(8) (2016) 3468-3479
 

Little is known about the chemical structure of purified extracellular polysaccharides from Phellinus sp., a fungal species with known medicinal properties. A combination of IR spectroscopy, methylation analysis and NMR were performed for the structural analysis of a purified extracellular polysaccharide derived from Phellinus sp. culture, denoted as SHP-1, along with an evaluation of the anti-aging effect in vivo of the polysaccharide supplementation. The structure of SHP-1 was established, with a backbone composed of →2,4)-α-D-glucopyranose-(1→ and →2)-β-D-mannopyranose-(1→ and two terminal glucopyranose branches. Biochemical analysis from mammalian animal experiments demonstrated that SHP-1 possesses the ability to enhance antioxidant enzyme activities, such as catalase (CAT) and superoxide dismutase (SOD) activities, Trolox equivalent antioxidant capacity (TEAC) in serum of D-galactose-aged mice, while reducing lipofuscin levels, another indicator of cell aging, indicating a potential association with anti-aging activities in a dose dependent manner. This compound had a favourable influence on immune organ indices, and a marked amelioration ability of histopathological hepatic lesions such as necrosis, karyolysis and reduced inflammation and apoptosis in mouse hepatocytes. These results suggest that SHP-1 has strong antioxidant activities and a significant protective effect against oxidative stress or hepatotoxicity induced by D-galactose in mice and it could be developed as a food ingredient or a pharmaceutical to prevent many age-associated diseases such as major depressive disorder and hepatotoxicity. To our knowledge, this is the first report on the antioxidant effects of a novel purified exopolysaccharide derived from Phellinus sp.

polysaccharide, extracellular, Antioxidant activity

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