Enhanced capture of bacteria and endotoxin by antimicrobial WLBU2 peptide tethered on polyethylene oxide spacers

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.

A critical review of hemoperfusion adsorbents: materials, functionalization and matrix structure selection

“…Besides, the hydrophilic polymer brushes were also used as surface coating materials due to their resistance to protein and cell adsorption. Schilke et al 74 showed tethering of antimicrobial peptide WLBU2 on pendant hydrophilic polymer brushes coating chains enhanced its ability to capture endotoxin in blood. With the development of natural hydrophilic polymer, the biodegradable and vivo-existing polymer showed a great potential in material modification to improve their stability, biocompatibility, pharmacokinetics, and thus biomedical functions.…”

Applicability of modified carbon sorbent for removing potentially toxic biologically active molecules of aromatic structure from blood plasma

“…One of the most common polymeric sorbents is a sorbent with Polymyxin B. Cartridges containing Polymyxin B are used during the treatment of the patients with multiple organ failure. [3][4][5] Another common non-selective sorbent is the highly porous polymer CytoSorb. It effectively removes a wide range of toxic substances from the blood reducing the cytokine storm which induces organ dysfunction in patients Applicability of modified carbon sorbent for removing potentially toxic biologically active molecules of aromatic structure from blood plasma with life-threatening inflammatory conditions.…”

Editorial: In Focus Issue on Bacterial-Surface Interactions

“…6 Both studies demonstrated the central role of biophysical techniques to both engineer and characterize biomaterials interfaces with quartz crystal microbalance, circular dichroism, XPS, and electrical impedance spectroscopy used to quantify the surface interactions and properties of the systems. The work of Raman et al 6 shows how antimicrobial peptides can be engineered into device coatings as capture agents for intact bacterial cells and the endotoxins associated with sepsis. Shahmiri et al 5 in turn created new insight into the design of surface-acting antimicrobial peptides, demonstrating that aromatic residues provide a membrane anchor for peptides which can provide a downstream effect.…”