Abstract:Acylation of antimicrobial peptides mimics the structure of the natural lipopeptide polymyxin B, and increases antimicrobial and endotoxin-neutralizing activities. In this study, the antimicrobial properties of lactoferrin-based LF11 peptides as well as blood compatibility as a function of acyl chain length were investigated. Beyond the classical hemolysis test, the biocompatibility was determined with human leukocytes and platelets, and the influence of antimicrobial peptides (AMPs) on the plasmatic coagulati… Show more
“…17 A). That heparin can neutralize the antimicrobial effect of synthetic cationic LF11 based AMPs has already been proven in a previous study 38 . Both unfractionated and fractionated (low molecular weight heparin) caused increased endotoxin recovery in plasma.…”
Section: Discussionmentioning
confidence: 56%
“…It is widely believed that they act through nonspecific binding to biological membranes, even though the exact nature of these interactions is currently unclear 36 , 37 . Because AMPs are cationic, binding to the polyanionic heparin is obvious 38 . Figure 3 Endotoxin neutralization caused by antimicrobial peptides.…”
Endotoxin neutralization, caused by plasma components, makes it difficult to detect endotoxins in human blood. In this study, we investigated which factors influence the recovery of endotoxins using limulus ameobocyte lysate (LAL)-based assays. The individual factors that were examined in more detail were lipoprotein content, type of blood anticoagulation, kinetics and serum levels of divalent cations. Furthermore, it was investigated whether there is a direct correlation between LAL activity and monocyte activation. We could show that polyanionic heparin increases endotoxin recovery in blood, while citrate anticoagulation promotes endotoxin neutralization. Furthermore, we could show that the endotoxin activity in human plasma and serum decreases strongly over time. Time-dependent endotoxin neutralization reaches its maximum after 4–6 h incubation. By means of filtration tests we could determine that endotoxins in the plasma bind to lipoproteins but do not influence their activity. Comparative measurements have shown that high LAL activity of endotoxins in plasma simultaneously possesses high monocyte activating properties in whole blood. For the maximum recovery of endotoxins in human blood the physiological calcium and magnesium concentrations are sufficient. In this study, it was shown that the endotoxin neutralizing plasma components have a molecular weight similar to β2-microglobulin (11.7 kDa). For the exact identification of the endotoxin neutralizing plasma components, which caused a modulation of the immunostimulating endotoxin activity, further investigations have to be carried out in the future.
“…17 A). That heparin can neutralize the antimicrobial effect of synthetic cationic LF11 based AMPs has already been proven in a previous study 38 . Both unfractionated and fractionated (low molecular weight heparin) caused increased endotoxin recovery in plasma.…”
Section: Discussionmentioning
confidence: 56%
“…It is widely believed that they act through nonspecific binding to biological membranes, even though the exact nature of these interactions is currently unclear 36 , 37 . Because AMPs are cationic, binding to the polyanionic heparin is obvious 38 . Figure 3 Endotoxin neutralization caused by antimicrobial peptides.…”
Endotoxin neutralization, caused by plasma components, makes it difficult to detect endotoxins in human blood. In this study, we investigated which factors influence the recovery of endotoxins using limulus ameobocyte lysate (LAL)-based assays. The individual factors that were examined in more detail were lipoprotein content, type of blood anticoagulation, kinetics and serum levels of divalent cations. Furthermore, it was investigated whether there is a direct correlation between LAL activity and monocyte activation. We could show that polyanionic heparin increases endotoxin recovery in blood, while citrate anticoagulation promotes endotoxin neutralization. Furthermore, we could show that the endotoxin activity in human plasma and serum decreases strongly over time. Time-dependent endotoxin neutralization reaches its maximum after 4–6 h incubation. By means of filtration tests we could determine that endotoxins in the plasma bind to lipoproteins but do not influence their activity. Comparative measurements have shown that high LAL activity of endotoxins in plasma simultaneously possesses high monocyte activating properties in whole blood. For the maximum recovery of endotoxins in human blood the physiological calcium and magnesium concentrations are sufficient. In this study, it was shown that the endotoxin neutralizing plasma components have a molecular weight similar to β2-microglobulin (11.7 kDa). For the exact identification of the endotoxin neutralizing plasma components, which caused a modulation of the immunostimulating endotoxin activity, further investigations have to be carried out in the future.
“…According to a previous report, these coral‐like patterns are derived from the aggregation of proteins. [ 24 ] Figure 3c shows the TEM characterization of the MXene covered with absorbed IL‐6, on which a layer of polymeric substance can be observed in marked contrast to pristine MXene (Figure 1b). Figure 3d shows a HRTEM image of MXene covered with IL‐6, on which the polymeric IL‐6 can be observed around the Ti 3 C 2 T x lattice structure.…”
During the global outbreak of COVID‐19 pandemic, “cytokine storm” conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3C2Tx MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin‐6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular‐level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin‐6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID‐19 patients.
“…This reduction in activity could be attributed to HSA binding, although this is unlikely because previous research has shown that the concentration of HSA is higher in plasma than in blood. It is also possible that the bacteriocin was degraded by blood constituents ( Svenson et al, 2007 ; Bottger et al, 2017 ; Harm et al, 2019 ). Previous work has found that the stability of peptides is greater in whole blood than in plasma and serum ( Bottger et al, 2017 ).…”
The membrane-bound protease Eep is an important virulence factor in pathogenic enterococci. The protein is involved in stress response via the RIP pathway which is crucial for pathogenic enterococci to evade host immune attacks during infection. Eep serves also as a receptor for the bacteriocins enterocin K1 and enterocin EJ97. The bacteriocins kill Enterococcus faecium and E. faecalis, respectively, and their antibiotic resistant derivatives including vancomycin resistant enterococci (VRE). This functional duality of Eep makes these two enterocins very promising as options in the prospective treatment of enterococcal infections because wildtype enterococcal cells (with an intact Eep) are sensitive to the bacteriocins while bacteriocin-resistant-mutants (without a functional Eep) become less virulent. As a first step to explore their therapeutic potential in the treatment of systemic enterococcal infections, we investigated the compatibility of the bacteriocins with human blood, and the phenotypic changes of eep-mutants toward different stress conditions. We found that the bacteriocins were compatible with blood, as they did not cause haemolysis and that the bacteriocins retained most of their antibacterial effect when incubated in blood. The bacteriocins were autoclavable which is a crucial criterium for the development of parenteral administration. Eep-mutants, which became resistant to the bacteriocin were, as expected, less capable to withstand stress conditions such as exposure to lysozyme and desiccation. Further, their ability to chain, a trait implicated in niche adaptation as well as being necessary for genetic transfer via conjugation, was also severely affected. Together, these results indicate that the bacteriocins are promising for treatment of VRE infection.
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