Endotoxin-like properties of a rhamnolipid exotoxin from Burkholderia (Pseudomonas) plantarii: immune cell stimulation and biophysical characterization
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Jörg Andrä
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.
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Artikel in diesem Heft
- Striated domains: self-organizing ordered assemblies of transmembrane α-helical peptides and lipids in bilayers
- Evolution of kallikrein-related peptidases in mammals and identification of a genetic locus encoding potential regulatory inhibitors
- Rec A-independent homologous recombination induced by a putative fold-back tetraplex DNA
- Spontaneous DNA-DNA interaction of homologous duplexes and factors affecting the result of heteroduplex formation
- DNA end-joining driven by microhomologies catalyzed by nuclear extracts
- A role for transmembrane domains V and VI in ligand binding and maturation of the angiotensin II AT1 receptor
- The zinc finger protein ZNF297B interacts with BDP1, a subunit of TFIIIB
- Pressure- and temperature-induced unfolding studies: thermodynamics of core hydrophobicity and packing of ribonuclease A
- Truncated PrPc in mammalian brain: interspecies variation and location in membrane rafts
- Endotoxin-like properties of a rhamnolipid exotoxin from Burkholderia (Pseudomonas) plantarii: immune cell stimulation and biophysical characterization
- p190-RhoGAP as an integral component of the Tiam1/Rac1-induced downregulation of Rho
- Human plasma adenosine deaminase 2 is secreted by activated monocytes
- Inhibition of mRNA deadenylation and degradation by different types of cell stress
- Identification of calpain cleavage sites in the G1 cyclin-dependent kinase inhibitor p19INK4d
- Identification of candidate substrates for ectodomain shedding by the metalloprotease-disintegrin ADAM8