ArticlePloS one2014
A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Antithrombin: An anticoagulant, anti-inflammatory and antibacterial serpin.Journal of thrombosis and haemostasis : JTH · 2020Article
- A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection.Nature microbiology · 2019Article
- Structural insights into the combinatorial effects of antimicrobial peptides reveal a role of aromatic-aromatic interactions in antibacterial synergism.The Journal of biological chemistry · 2019Article
- An antibacterial and biocompatible piperazine polymer.RSC advances · 2019Article
- Antiinflammatory peptides: current knowledge and promising prospects.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides.Nature communications · 2018Article
- TFPI-2 Protects Against Gram-Negative Bacterial Infection.Frontiers in immunology · 2018Article
- Heparinase Is Essential for Pseudomonas aeruginosa Virulence during Thermal Injury and Infection.Infection and immunity · 2018Article
- Immunohaemostasis: a new view on haemostasis during sepsis.Annals of intensive care · 2017Review
- Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects.Scientific reports · 2017Article
- Piscidin-1-analogs with double L- and D-lysine residues exhibited different conformations in lipopolysaccharide but comparable anti-endotoxin activities.Scientific reports · 2017Article
- Role of Aromatic Amino Acids in Lipopolysaccharide and Membrane Interactions of Antimicrobial Peptides for Use in Plant Disease Control.The Journal of biological chemistry · 2016Article
- Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.