Lipopolysaccharides

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Lipopolysaccharide (LPS) endotoxins are characteristic Gram-negative outer-cell components which are produced by many cyanobacteria. Although LPS have been characterized and found to be toxic to laboratory animals after isolation from cyanobacteria, their toxicity to rodents is less potent than the endotoxins of enteric pathogens such as Salmonella Typical symptoms of animals suffering from LPS intoxication include vomiting, diarrhoea, weakness and death after hours rather than minutes. 

Cell wall Peptidoglycan a rigid framework of polysaccharide cross-linked by short peptide chains. Some bacteria possess a lipopolysaccharide- and protein-rich outer membrane. Mechanical support, shape, and protection against swelling in hypotonic media. The cell wall is a porous nonselective barrier that allows most small molecules to pass. 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

As shown in Figure 9.24, the outer membrane of Gram-negative bacteria is coated with a highly complex lipopolysaccharide, which consists of a lipid group (anchored in the outer membrane) joined to a polysaccharide made up of long chains with many different and characteristic repeating structures... 

FIGURE 9,24 Lipopolysaccharide (LPS) coats the outer membrane of Gram-uegative > bacteria. The lipid portion of the LPS is embedded iu the outer membrane and is linked to a complex polysaccharide. 

Figure 1 Structure of lipopolysaccharide (LPS) from gram-negative Salmonella species.

E. Th. Rietschel, L. Brade, B. Lindner and U. Zahringer. Bacterial Endotoxic Lipopolysaccharides. Vol. I. Molecular Biochemistry and Cellular Biology (D. C. Morrison, and J. L. Ryan, eds.) CRC Press, Boca Raton, Florida, p. 3-41 (1992). 

Many different types of carbohydrate-containing molecules are located on the surface of microbial cells. Some of these are components of die microbial cell wall and are limited to certain types of micro-organisms such as bacterial peptidoglycan, lipopolysaccharides, techoic adds and yeast mannans. Other polysaccharides are not... 

Autoimmune Disease. Figure 2 Generation of autoreactivity. APC, antigen presenting cell IFN, interferon LPS, lipopolysaccharide MHC, major histocompatibility complex T, T-lymphocyte TCR, Tcell (antigen) receptor TLR, toll like receptors. For details see text. 

Endotoxins are the lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria. They trigger inflammatory reactions in the infected organism, activate complement and cause fever or even a septic shock. They act on toll-like receptors. 

Gram-negative (whole organisms peptidoglycans lipopolysaccharides [lipid A])... 

Induced by bacterial lipopolysaccharides or immune cytokines in macrophages, smooth muscle cells, and glia cells. Ca2+ is not required for the enzyme activation. 

Mice that are homozygous for a disrupted Bx or B2 receptor gene are healthy, fertile and normotensive. In Bx-deficient mice, bacterial lipopolysaccharide-induced hypotension is diminished and the recruitment of polymorphonuclear leukocytes to the sites of tissue injury is impaired, and the animals show signs of hypoalgesia. Deletion of the B2 gene in mice leads to salt-sensitive hypertension and altered nociception. 

The genes coding for CETP and PLTP belong to one gene family, which also includes lipopolysaccharide-binding-protein (LBP) and bactericidal/permeability-increasing-protein (BPI). This common descent not only becomes clear from a considerable sequence similarity (45-65% homology at the cDNA level), but also from substantial conservation of exon/intron transitions. 

A lipopolysaccharide (LPS) is any compound consisting of covalently linked lipids and polysaccharides. The term is used more frequently to denote a cell wall component from Gram-negative bacteria. LPS has endotoxin activities and is a polyclonal stimulator of B-lymphocytes. 

Inducible NO synthase (iNOS) is usually not constitutively expressed, but can be induced in macrophages by bacterial lipopolysaccharide (LPS), cytokines and other-agents. Although primarily identified in macrophages, expression of the enzyme can be stimulated in virtually any cell or tissue, provided the appropriate inducing agents have been identified (for review see [1] and [3]). 

CD C14 C14.012 Caspase-11 Potential drug target in lipopolysaccharide-induced septic shock... 

Lipid Transfer Proteins Lipidation Lipopolysaccharide Lipoprotein Lipase... 

Shortly afterwards, Westphal, Liideritz, and their coworkers using the newly developed method of paper chromatography, found a new class of sugars in lipopolysaccharides (LPS) from Gram-negative bacteria, and identified them as 3,6-dideoxyhexoses. This work is summarized in Ref. 4. These discoveries initiated more-systematic investigations of hydrolyzates from bacterial polysaccharides, and a number of new monosaccharides were completely or partially identified. This development has been summarized by Ashwell and Hickman. ... 

Abbreviations LPS, lipopolysaccharide EPS, extracellular polysaccharide Photosynth., photosynthetic prokaryote. 

Other toxins that show low lethal toxicity to laboratory test animals include lipopolysaccharide endotoxin produced as part of the cell wall by all cyanobacteria 11) and certain toxins of some cyanobacteria suspected of causing contact irritation in recreational water supplies 4,12 Carmichael and Codd, unpublished results). 

Boddeke EW, Meigel 1, Frentzel S, Biber K, Renn LQ, Gebicke-Harter P (1999) Functional expression of the fractaUdne (CX3C) receptor and its regulation by lipopolysaccharide in rat microglia. Eur J Pharmacol 374 309-313... 

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