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- Title
Endotoxin-like properties of a rhamnolipid exotoxin from Burkholderia ( Pseudomonas) plantarii: immune cell stimulation and biophysical characterization.
- Authors
Andrä, Jörg; Rademann, Jörg; Howe, Jörg; Koch, Michel H. J.; Heine, Holger; Zähringer, Ulrich; Brandenburg, Klaus
- Abstract
Here we report on the purification, structural characterization, and biological activity of a glycolipid, 2- O-α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-α( 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 α, 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.
- Subjects
ENDOTOXINS; GLYCOLIPIDS; PSEUDOMONAS; TUMOR necrosis factors; SEPSIS
- Publication
Biological Chemistry, 2006, Vol 387, Issue 3, p301
- ISSN
1431-6730
- Publication type
Article
- DOI
10.1515/BC.2006.040