Lipopolysaccharide , bacterial cells

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... 

Carbohydrates related to membranes can be found as lipopolysaccharides or as parts of glycoproteins. Sugars are often characteristic determinants of cell surfaces (see below). The great majority of carbohydrates are found in the outer leaflet of a membrane, resulting in an asymmetrical structure. This is especially true for many plasma membranes and the outer membrane of Gram-negative bacterial cells (see below). 

Among the important glycolipids, which are combinations of carbohydrate and lipid, are the cerebrosides and gangliosides. These are constituents of brain and nervous tissue and are usually considered with lipids because they are water-insoluble. Water-soluble polymers of high relative molecular mass containing lipid and carbohydrate, known as lipopolysaccharides, are found in bacterial cell walls. 

Huang etal. (2002) prepared an antibody array for the simultaneous detection of 43 cytokines. They were able to verify the down-regulation of MCP-1 cytokine in transfected cells (human glioblastoma cells transfected with cx43 expression vector) relative to control cells. The antibody array is an emerging technology. In at least one study based upon the use of a commercial membrane format, the cytokine microarray failed to accurately determine cytokine levels in bacterial and lipopolysaccharide (LPS)-stimu-lated whole human blood (Copeland, 2004). 

One of the most serious consequences of (Gram-negative) bacterial infection is the possible development of septic shock. This is caused by the release of lipopolysaccharide (LPS endotoxin) from the bacterial cell surface. Various anti-LPS monoclonals (mainly targeted at its lipid A component Chapter 3) have been developed. It is hoped that administration of such monoclonals to affected individuals would effectively mop up free LPS, hence ameliorating the severity of the condition. Most trial results to date have proved disappointing in this regard. 

Endotoxins are bacterial cell envelope constituents that, when present in pharmaceutical products, cause pyrogenic reactions sometimes resulting in lethality. The toxicity of endotoxins is directly related to their chemical composition. However, the viability of the organism is irrelevant since endotoxin derived from dead or live microbes is equally active. The classical endotoxin is lipopolysaccharide (LPS). However, peptidoglycan (PG) also displays endotoxin-like activities. LPS is found only in gram-negative bacterial outer membranes, while PG is present in the cell... 

Myeloma proteins occur in animal tumors of various types. The synthesis of these proteins can be induced in some experimental animals by injection of mineral oil, or the implantation of plastic discs.161 Myeloma proteins were shown to possess antibody activity, with specificity for different types of substances.161 Some of these proteins were found to combine with such carbohydrates as bacterial, cell-wall polysaccharides, lipopolysaccharides, dextrans, levans, and galactans.162 Myeloma proteins that combine with galactans or dextrans possess anti-galactan activity,163,164 or anti-dextran activity,165-167 and have been studied most extensively. 

In the polymers of groups (1) and (2), polysaccharide chains composed of oligosaccharide repeating-units (sometimes, partially modified) are usually linked to a unique oligosaccharide unit present near the point of attachment of the chain to another polymeric chain, or to a lipid anchor. This unit is called the linkage region in the polymers of bacterial cell-wall, and the core region in lipopolysaccharides. 

Lipopolysaccharides form a class of macromolecules unique to Gramnegative bacteria. They are of great compositional and structural diversity, and yet, they are built up according to a common architectural principle. With few exceptions, lipopolysaccharides are biologically highly active substances. Lipopolysaccharides have been called endotoxins because of their toxic properties. Due to the antigenic properties which they confer to the surface of the bacterial cell, they are also termed O antigens. 

Aside from the expression of histidine mutations that are easily detected, other properties have been built into the Salmonella strains by mutation to increase their sensitivity. The strains cure defective in DNA excision repair (uvrB). In this case, the increased sensitivity probably is due to the failure to remove some DNA adducts that could lead to mutation. The strains also possess a mutation (rfa) that removes part of the lipopolysaccharide barrier of the bacterial cell wall and thereby makes the cells more permeable to some chemicals. Finally, Salmonella strains TA98 and TA100 contain the R-factor plasmid pkMIOl,277 which increases sensitivity probably by increasing the activity of an error-prone DNA-repair system. 

Treg cells are equipped with TLR 4, TLR 5, TLR 7, and TLR 8 receptors. Bacterial LPS (lipopolysaccharide) may act on TLR 4, either directly or not, through APC cells. Indirect stimulation with the use of Bordetella pertussis leads to the release of IL 10 (Higgins et al., 2003), while the use of Candida albicans additionally extends life expectancy of CD4+ CD25+ lymphocytes (Netea et al., 2004)... 

Bos, M.P., Tefsen, B., Geurtsen, J., Tommassen, J. Identification of an outer membrane protein required for the transport of lipopolysaccharide to the bacterial cell surface. Proc Natl Acad Sci... 

Blood-brain barrier Treatment of central nervous system infections, such as meningitis, depends on the ability of a drug to penetrate into the cerebrospinal fluid (CSF). The blood-brain barrier (see p. 8) ordinarily excludes many antibiotics. However, inflammation facilitates penetration and allows sufficient levels of many (but not all) antibiotics to enter the CSF. [Note For cure of meningitis, it is important that a bactericidal rather than a bacteriostatic effect is achieved in the CSF. Yet, this is not without its problems, since rapid bacteriolysis in the infected CSF will liberate high concentrations of bacterial cell walls and lipopolysaccharide that can exacerbate the inflammation. This has led to the use of adjunctive (simultaneous administration of) corticosteroids, which diminish the inflammatory process and neurologic sequelae.]... 

---