Endotoxins: Lipopolysaccharides of Gram-Negative Bacteria

Abstract

Endotoxin refers lipopolysaccharide that constitutes the outer leaflet of the outer membrane of most Gram-negative bacteria. Lipopolysaccharide is comprised of a hydrophilic polysaccharide and a hydrophobic component known as lipid A which is responsible for the major bioactivity of endotoxin. Lipopolysaccharide can be recognized by immune cells as a pathogen-associated molecule through Toll-like receptor 4. Most enzymes and genes related to the biosynthesis and export of lipopolysaccharide have been identified in Escherichia coli, and they are shared by most Gram-negative bacteria based on available genetic information. However, the detailed structure of lipopolysaccharide differs from one bacterium to another, suggesting that additional enzymes that can modify the basic structure of lipopolysaccharide exist in bacteria, especially some pathogens. These structural modifications of lipopolysaccharide are sometimes tightly regulated. They are not required for survival but closely related to the virulence of bacteria. In this chapter we will focus on the mechanism of biosynthesis and export of lipopolysaccharide in bacteria.

IntracellularShigellaremodels its LPS to dampen the innate immune recognition and evade inflammasome activation

“…However, LPS can also elicit an host reaction because it is a major mediator of pathologic processes (4). The strength of the innate immune response to LPS can be modulated by its chemical structure; specifically, a fine tuning of the lipid A structure can significantly affect the immunostimulatory properties of the whole LPS molecule (5,6). There is a strong correlation between the number of acyl chains of lipid A and the immunological response via the TLR4 pathway.…”

Regulation of Caenorhabditis elegans and Pseudomonas aeruginosa machinery during interactions

“…In the present study, we found higher concentrations of LPS (C2 mg/ml) were toxic to the animal. Recent evidence suggested that P. aeruginosa LPS displayed heterogeneity in nature between the strains and was able to change its own LPS compositions during host interactions (Bryant et al 2010;Wang and Quinn 2010). The present study revealed that PAO1 had dramatically changed its own LPS at the polysaccharide (1,200-900 cm -1 ) and fatty acid (3,000-2,800 cm -1 ) regions during the host contact, which was further confirmed by FTIR, PCA and also by X-Ray diffraction studies.…”

Ralstonia solanacearum RSc0411 (lptC) is a determinant for full virulence and has a strain-specific novel function in the T3SS activity

“…1, the organization of the DUF1239-related gene cluster is mostly conserved in the analysed bacteria, except for the absence of RSc0412 (kdsC/ybrI) in a few bacteria. In E. coli, the five genes included in this cluster are involved in LPS biosynthesis (KdsD, KdsC) or LPS transport (LptC, LptB, LptA) (Wang & Quinn, 2010) and are organized into three operons ( Fig. 1; Sperandeo et al, 2007).…”

“…Rough (R-)LPS are composed of the hydrophobic membrane-anchored lipid A moiety and the short core oligosaccharide, and the addition of variable O-antigen polysaccharide chain onto R-LPS leads to the formation of the complete structure of smooth (S-)LPS. The synthesis, assembly and transport of LPS components are well studied in Escherichia coli (Raetz & Whitfield, 2002;Wang & Quinn, 2010;Sperandeo et al, 2011). R-LPS are synthesized via a conserved pathway, which involves proteins on the cytoplasmic surface of the inner membrane (IM), then transported by MsbA across the IM where ligation of R-LPS to O-antigen is triggered by WaaL to form S-LPS.…”