Jörg Andrä, Jörg Rademann, Jörg Howe, Michel H.J. Koch, Holger Heine, Ulrich Zähringer, Klaus Brandenburg
Endotoxin-like properties of a rhamnolipid exotoxin from Burkholderia (Pseudomonas) plantarii: immune cell stimulation and biophysical characterization
Here we report on the purification, structural characterization, and biological activity of a glycolipid, 2-O-?-L-rhamnopyranosyl-?-L-rhamnopyranosyl-?(R)-3-hydroxytetradecanoyl-(R)-3-hydroxytetradecanoate (RL-2,214) produced by Burkholderia (Pseudomonas) plantarii. RL-2,214 is structurally very similar to a rhamnolipid exotoxin from Pseudomonas aeruginosa and identical to the rhamnolipid of Burkholderia pseudomallei, the causative agent of melioidosis. Interestingly, RL-2,214 exhibits strong stimulatory activity on human mononuclear cells to produce tumor necrosis factor ?, the overproduction of which is known to cause sepsis and the septic shock syndrome. Such a property has not been noted so far for rhamnolipid exotoxins, only for bacterial endotoxins (lipopolysaccharide, LPS). Consequently, we analyzed RL-2,214 with respect to its pathophysiological activities as a heat-stable extracellular toxin. Like LPS, the cell-stimulating activity of the rhamnolipid could be inhibited by incubation with polymyxin B. However, immune cell activation by RL-2,214 does nor occur via receptors that are involved in LPS (TLR4) or lipopeptide signaling (TLR2). Despite its completely different chemical structure, RL-2,214 exhibits a variety of endotoxin-related physicochemical characteristics, such as a cubic-inverted supramolecular structure. These data are in good agreement with our conformational concept of endotoxicity: intercalation of naturally originating virulence factors into the immune cell membrane leads to strong mechanical stress on integral proteins, eventually causing cell activation.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 387, 03/2006
Pages: 301 - 310
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