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Published on: December 3, 2020
Enhanced capture of bacteria and endotoxin by antimicrobial WLBU2 peptide tethered on polyethylene oxide spacers
Ramya Raman1, Miranda A Raper1, Erik Hahn1
1Department of Chemical, Biological and Environmental Engineering, Oregon State University, 116 Johnson Hall, Corvallis, Oregon 97331.
Abstract:
Severe sepsis is a life threatening immune response that may be caused by endotoxins (lipopolysaccharides) in circulating bacterial cell wall fragments. Hemoperfusion through a sorbent column coated with the antimicrobial peptide polymyxin B (PMB) is a promising treatment for sepsis. However, PMB is cytotoxic and neurotoxic, and is a membrane disruptor that may fragment endotoxin vesicles. In addition, the blood is not protected from nonspecific interactions with the synthetic surface of the solid support. These effects may be responsible for the variety of undesirable clinical outcomes, including nonspecific adsorption of proteins, blood cell damage, platelet activation, and a lack of clear evidence of efficacy of the current hemoperfusion products. An alternative endotoxin-binding agent is WLBU2, a synthetic cationic amphiphilic peptide that exhibits better selectivity for bacterial cell membranes and reduced host cell cytotoxicity. Tethering the peptide at the periphery of a hydrophilic polyethylene oxide (PEO) brush should also mask the underlying surface, preventing cell and protein adsorption, and is expected to increase the solvent accessibility and molecular mobility of the tethered peptides. WLBU2 tethered on pendant PEO chains exhibited significantly greater capture of intact bacterial cells and endotoxin than surface-immobilized WLBU2. Tethered WLBU2 also captured amounts of endotoxin comparable to PMB. These results suggest that PEO-tethered WLBU2 coatings may be safer and more effective than the state-of-the-art PMB-based technology.
Insights
A new peptide, WLBU2, offers a safer and potentially more effective treatment for severe sepsis by binding endotoxins. Unlike current polymyxin B treatments, WLBU2 shows reduced toxicity and better endotoxin capture when tethered to polyethylene oxide brushes.
Area of Science:
- Biomedical Engineering
- Infectious Disease Research
- Materials Science
Background:
- Severe sepsis, a life-threatening immune response, is often caused by endotoxins from bacterial cell walls.
- Current hemoperfusion treatments using polymyxin B (PMB) face limitations due to PMB's cytotoxicity and nonspecific interactions with blood components.
- These limitations lead to adverse clinical outcomes and unclear efficacy of existing PMB-based hemoperfusion products.
Purpose of the Study:
- To evaluate WLBU2, a synthetic peptide, as a safer and more effective alternative to PMB for endotoxin capture in sepsis treatment.
- To investigate the performance of WLBU2 when tethered to polyethylene oxide (PEO) brushes for improved hemoperfusion.
Main Methods:
- Synthesized and characterized WLBU2 peptide and PEO-tethered WLBU2 coatings.
- Compared the endotoxin and bacterial cell capture efficiency of PEO-tethered WLBU2 with surface-immobilized WLBU2 and PMB-coated materials.
- Assessed the potential for nonspecific adsorption and host cell interactions.
Main Results:
- PEO-tethered WLBU2 demonstrated significantly higher capture of intact bacterial cells and endotoxins compared to surface-immobilized WLBU2.
- WLBU2 coatings captured amounts of endotoxin comparable to PMB.
- The PEO brush structure effectively masked the underlying surface, reducing nonspecific adsorption and potential cell damage.
Conclusions:
- PEO-tethered WLBU2 presents a promising advancement in sepsis treatment, offering improved endotoxin binding with reduced cytotoxicity.
- This novel approach may overcome the limitations of current PMB-based hemoperfusion technologies.
- WLBU2-coated materials show potential for safer and more effective management of severe sepsis.

