Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins.

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Initial responses to endotoxins and Gram-negative bacteria.

Structural biology of the LPS recognition

https://kops.uni-konstanz.de/bitstream/handle/123456789/8098/A_conserved_structural_motif_for_lipopolysaccharide_recognition_by_procaryotic_and_eucaryotic_proteins.pdf;sequence=1

A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins

Cholic acid derivatives appended with amine groups have been prepared for use as permeabilizers of the outer membranes of Gram-negative bacteria. These compounds interact synergistically with antibiotics such as erythromycin and novobiocin to inhibit growth of Gram-negative bacteria. When a hydrophobic chain is included on the permeabilizers, they can be converted into potent antibiotics. The role of the hydrophobic chain is to facilitate self-promoted transport of the cholic acid derivatives across the outer membrane of Gram-negative bacteria. These compounds share activities found with polymyxin B and derivatives.

Incremental Conversion of Outer-Membrane Permeabilizers into Potent Antibiotics for Gram-Negative Bacteria

The present invention provides novel peptides derived from portions of the sequence of amino acids 95-104 of lipopolysaccharide binding protein (LBP). The invention also provides pharmaceutical compositions comprising the peptides of the invention, and diagnostic and therapeutic methods utilizing the peptides and pharmaceutical compositions of the invention.

Novel peptides useful for inhibiting binding of lipopolysaccharides (lps) by lipopolysaccharide binding protein (lbp)

Lipopolysaccharide (LPS) Neutralizing Peptides Reveal a Lipid A Binding Site of LPS Binding Protein

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Novel peptides useful for inhibiting binding of lipopolysaccharides (lps) by lipopolysaccharide binding protein (lbp)

Lipopolysaccharide (LPS) Neutralizing Peptides Reveal a Lipid A Binding Site of LPS Binding Protein