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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #82010
Title: ENDOTOXIN VACCINES

Author
item KEHRLI JR, MARCUS

Submitted to: Institute for International Cooperation in Animal Biologics
Publication Type: Proceedings
Publication Acceptance Date: 6/2/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Endotoxins are constituents of the cell wall of gram-negative bacteria. Chemically, endotoxins are lipopolysaccharides of a molecular weight ranging from 1 to 20 x 10**6 daltons. Lipopolysaccharide (LPS) is a unique component of the gram-negative bacterial cell wall outer membrane (OM). This OM is exterior to the peptidoglycan layer of the bacterial cell wall. The general 3-part design of LPS is illustrated below and is made up as follows: Part 1 is the most proximal portion of the molecule and is composed of a hydrophobic region known as lipid A; Part 2 is a core polysaccharide that contains some unique sugars (2-keto-3-deoxy-octonic acid, heptose, ethanolamine, galactose, N-acetylglucosamine and glucose); and Part 3 is a hydrophilic polysaccharide of variable size that is also known as the O-antigen. The lipid A backbone and the proximal portion of the core backbone contain a number of charged groups giving this region of LPS an anionic nature. Loss of the O-antigen will most generally reduce the virulence of a strain (presumably due to the role of the O antigen in preventing phagocytosis). The lipid A portion of the molecule, however, mediates much of the pathophysiological effects of LPS on cells through its ability to activate protein kinase C enzymes in cells. The hydrophobic nature of lipid A allows this portion of the LPS molecule to embed itself in the phospholipid bilayers of cells and mimic the effects of diacylglycerol in the cell. Research in the early 1960's identified a unique strain of Escherichia coli that had two mutations in the LPS biosynthetic pathway. This finding along with the findings of various rough (R) mutants of Salmonella sp were the basis for nearly 30 years of research on use of rough mutants as vaccines for endotoxemia in humans and animals.