Kdo2-Lipid A

Lipidomics Gateway (27 May 2010) [doi:10.1038/lipidmaps.2010.18]

A structurally defined component of lipopolysaccharide – present in Gram-negative bacteria – this saccharolipid triggers the innate immune response.

The structure of Kdo2-Lipid A. Visit Kdo2-Lipid A in the LIPID MAPS structure database for more molecular information.

Most Gram-negative bacteria have lipopolysaccharide (LPS) on their outer surface. Consisting of a lipid anchor (lipid A) and two variable oligosaccharide regions (the core and the O-antigen), it is the lipid A component that is an endotoxin. At low levels, endotoxin-mediated activation of Toll-like receptor 4 (TLR4) is beneficial, because downstream signaling pathways mobilize defense mechanisms against the invading bacteria. Severe infections can however cause excessive endotoxin exposure, which can lead to shock, multiple organ failure and death.

The transcription rates of hundreds of genes are changed by LPS exposure, producing complex responses. Attempts to characterize LPS-induced sepsis are also complicated by the heterogeneity of the core and O-antigen glycan chains, which make it impossible to directly quantify LPS in samples.

Kdo2-Lipid A is an intermediate in the synthesis of LPS. It has two 3-deoxy-D-manno-octulosonic acid (Kdo) sugar residues in place of the core, and has no O-antigen. The LIPID MAPS consortium developed a method to produce large amounts of purified Kdo2-Lipid A from mutant Escherichia coli. The defined chemistry and reproducibility of the substance make it suitable for quantitative mass spectrometry measurements, and its ability to activate TLR4 is comparable to that of native LPS. Data from time course experiments profiling macrophage lipid or gene expression levels after exposure to Kdo2-Lipid A can be found here, and standardized protocols are available.

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