Gram -negative bacteria pyrogens

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 high space-time yields are the result of a doubling time of only 30 min and its applicability for high cell-density cultures. However, it is hardly possible to excrete overexpressed proteins into cultivation media. In addition, accumulation of pyrogenic lipopoly-saccharides in its outer membrane (a distinctive feature of Gram-negative bacteria) make additional purification steps necessary if pharmaceutical proteins are produced by E. coli [29]. 

Excipients derived from bacterial transformation or enzymatic processes, such as sugars (e.g., mannitol or dextrose), pose special concerns due to potential contamination by endotoxins. Endotoxins, or pyrogens, are lipopolysaccharides from gram-negative bacteria that can induce severe fever upon parenteral administration. Parenteral products have different limits for allowable endotoxin levels.57... 

The main problems from microbial metabolites found in medicines are caused by pyrogens, which are lipopolysaccharides (usually). These are derived from Gram-negative bacteria, and can induce acute shock. Other compounds are the mycotoxins formed by fungi, which may be found in medicines derived from natural products. These are considered in more detail in the chapter on food. 

C68H130N2O23P2. Mr 1405.73, amorphous solid. Component of glycophospholipids of Gram-negative bacteria. L. A is important for the toxicity, pyrogenicity, and adjuvant activities of the bacteria. Variants of the formula shown from Escherichia and Proteus are ac-ylated at the OH groups of the tetradecanoyl units. 

The use of solvents to recover PHA is one of the oldest and commonly used methods. Firstly, it affects the cell membrane permeability and then it dissolves the PHA. However, PHAs may be contaminated by lipopoly-saccharides (LPS) during the extraction process if solvents are used. LPS is an component from the cell wall of the Gram-negative bacteria, which is pyrogenic in nature.For medical purposes, PHAs need to be highly pure, especially with respect to pyrogenic compounds. LPS are considered the main source of pyrogenic contamination. ... 

Endotoxin is a term often used synonymously with lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Endotoxin has been estimated to make up between 3 and 4% of the dry weight of Escherichia coli K12. The LPS molecule consists of a Lipid A component anchored in the outer membrane. This is attached to a series of saccharide units specific for different strains of Gram-negative bacteria. LPS is extremely heat stable and needs to be heated to 180 °C for three hours to ensure inactivation. When injected into the bloodstream, it activates the alternative complement pathway and produces a pyrogenic reaction. Studies on laboratory animals have shown that it can produce severe reactions when inhaled in microgram quantities. ... 

The gram-negative cell wall contains only a shallow peptidoglycan layer. On the outer side of this layer is the outer membrane, a complex stmcture consisting of four major components phospholipids, lipopolysaccharide, proteins (e.g., porins), and lipoprotein. Lipolysaccharide (endotoxin) is responsible for the pyrogenicity of the gram-negative bacteria. 

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