Outer lipopolysaccharides

The identification of terminal complexes in the Gram-negative bacterium Acetobacter xylinum now appears to be in doubt. Previously, a single linear row of particles observed on the outer lipopolysaccharide membrane... 

DePamphiHs, M.L. and Adler, J. (1971). Attachment of flagellar basal bodies to the cell envelope Specific attachment to the outer, lipopolysaccharide membrane and the cytoplasmic membrane./. Bacteriol. 105, 396-407. 

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. 

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. 

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. 

The Gram-negative cell envelope (Fig. 1.4) is even more complicated essentially, it contains lipoprotein molecules attached covalently to the oligosaccharide backbone and in addition, on its outer side, a layer of lipopolysaccharide (LPS) and protein attached by hydrophobic interactions and divalent metal cations, Ca and Mg. On the inner side is a layer of phospholipid (PL). 

T. Ojanen, 1. M. Helander, K. Haahtela, T. K. Korhnonen, and T. Laak.so, Outer membrane proteins and lipopolysaccharides in pathovars of Xanthomonas camp-estris, Appl. Environ. Microbiol. 59 4143 (1993). 

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]. 

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). 

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. 

Chemical nature Lipopolysaccharide (LPS), component of the bacterial outer membrane Proteins... 

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...

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... 

Lipopolysaccharides are the dominant surface feature of the outer membrane of gram-negative bacteria such as Escherichia coli and Salmonella ty-phimurium. These molecules are prime targets of the antibodies produced by the vertebrate immune system in response to bacterial infection and are therefore important determinants of the serotype of bacterial strains (serotypes are strains that are distinguished on the basis of antigenic properties). The lipopolysaccharides of S. typhimurium contain six fatty acids bound to two... 

FIGURE 7-32 Bacterial lipopolysaccharides. (a) Schematic diagram of the lipopolysaccharide of the outer membrane of Salmonella ty-phimurium. Kdo is 3-deoxy-o-manno-octulosonic acid, previously called ketodeoxyoctonic acid Hep is L-glycero-D-mannoheptose AbeOAc is abequose (a 3,6-dideoxyhexose) acetylated on one of its hydroxyls. There are six fatty acids in the lipid A portion of the molecule. Different bacterial species have subtly different lipopolysaccharide structures, but they have in common a lipid region (lipid A), a core oligosaccharide, and an "O-specific" chain, which is the prin-... 

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