Gram-negative bacteria, lipopolysaccharides

Lipid A is the endotoxic principle of Gram-negative bacteria lipopolysaccharide. Its structure varies between bacteria. Sepsis could equally also be classed as immunomodulatory. 

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... 

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. 

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. 

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. ... 

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

The surface structure of gram-negative bacteria (these are not stained by Gram s method and must be stained red with carbol fuchsin) is more diversified. It consists of an outer membrane whose main building unit is a lipopolysaccharide together with phospholipids and proteins. The actual cell... 

In Gram-negative bacteria the cell wall is only about 3 nm thick, and located in the extended periplasmatic space between the inner membrane (IM) and an additional outer membrane (OM). The lipid monolayer in the outer leaflet of the OM contains about 90% lipopolysaccharides (LPS). LPS consist of Lipid A and an oligosaccharide component, which is highly specific for individual bacterial species and phenotypes [108, 114]. 

The interaction between melittin (a 26 a.a. peptide that exhibits potent anti-microbial activity)90 92 and lipopolysaccharides (the major constituent of the outer membrane of the Gram-negative bacteria) has been studied by NMR. It was demonstrated that the C-terminus of melittin adopts a helical structure in the complex with LPS, while the Y-terminus appears in an extended conformation. STD experiments permitted to identify those residues of melittin in close proximity with LPS, which appeared to be located at the C-terminus and thus, engaged in the formation of helical structure. 

Occurrence and Linkages of KDO in Lipopolysaccharides from Gram-Negative Bacteria... 

Lipopolysaccharides (LPS) P-hydroxy-acids Gram-negative bacteria... 

Some examples of transformations involving carbonyl ylides are listed in Table 4.20. Entry 1 illustrates the conversion of P-acyloxy-a-diazoesters into a-acyloxyacrylates by ring fission of a cyclic carbonyl ylide [978]. This reaction has been used for the synthesis of the natural aldonic acid KDO (3-deoxy-Z)-manno-2-octulosonic acid), which is an essential component of the cell wall lipopolysaccharide of gram-negative bacteria (Figure 4.15). 

Arnold and Brown (1978) reported on the possibility that bacterial endotoxins, which are widespread, could result in hypersensitivity to histamine. These compounds are complex, heat-stable, lipopolysaccharide materials produced primarily by Gram-negative bacteria. They also reported that endotoxin is known to be capable of inducing histamine release in animals (sometimes called endotoxin shock) similar to that seen in anaphylaxis. Baranowski et al. (1990), however, reported extremely low levels of endotoxin in both good tuna and tuna known to have caused illness in humans. 

Endotoxin. Endotoxin is the lipopolysaccharide that comprises a major portion of the cell wall of the gram-negative bacteria. The endotoxins from each species of bacteria are different but the lipid A moiety is similar for the Enterobacterlaceae, and has a similar series of biological actions regardless of its source. The lipid A material is different in some of the gram-negative rods present in cotton (i.e. in the Pseudomonas species). This variety of compounds makes quantitation of endotoxin difficult. Hence, it is usually measured by its biological activity as compared to a standard endotoxin (usually that of E. coll). (See Table VIII.)... 

Figure 3.37. Structure of a generalized lipopolysaccharide (LPS) molecule. LPS consitutes the major structural component of the outer membrane of Gram-negative bacteria. Although LPS of different Gramnegative organisms differ in their chemical structure, each consists of a complex polysacharide component, linked to a lipid component. Refer to text for specific details...

Figure 12.6 Colorimetric response (CR) values obtained upon exposure of the liposome array to lipopolysaccharides from different Gram negative bacteria for ( ) Trp and ( ) Tyr. AU values are the average of at least four experiments. RT, room temperature [liposome] w 0.6 mM, [LPS] 2.2mg/mL, [SDS] = 2 mM, [EDTA] = 1 mM. See supporting information for details.

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