ArticleEMBO molecular medicine2020
Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- Exploitation of cholesterol-dependent cytolysins for targeted biosensing and therapeutic systems.Drug delivery and translational research · 2026Review
- Challenges and opportunities in the management of severe pneumonia. Key concepts from the Seventh Annual Meeting of Spanish Experts 2025.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026Review
- The mannose receptor on sinusoidal lining cells mediates two-step bacterial clearance in the human spleen.Nature communications · 2026Article
- Bacterial pore-forming toxins: mechanisms and implications for host immunity.Bioscience reports · 2026Review
- C-Type lectin receptors as key modulators of intestinal inflammation: insights into IBD pathogenesis and therapy.FEMS microbiology letters · 2026Review
- Mucosal immunotherapy targeting APC in lung disease.Journal of inflammation (London, England) · 2025Review
- Streptococcus pneumoniae epidemiology, pathogenesis and control.Nature reviews. Microbiology · 2025Review
- A Low-Cost Electrochemical Cell Sensor Based on MWCNT-COOH/α-FeNanomaterials (Basel, Switzerland) · 2025Article
- Pneumococcal pneumonia is driven by increased bacterial turnover due to bacteriocin-mediated intra-strain competition.Communications biology · 2024Article
- Streptolysin O accelerates the conversion of plasminogen to plasmin.Nature communications · 2024Article
- Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection.iScience · 2024Article
- The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.International journal of molecular sciences · 2023Review
- Cholesterol dependent cytolysins and the brain: Revealing a potential therapeutic avenue for bacterial meningitis.AIMS microbiology · 2023Review
- Live-cell imaging reveals single-cell and population-level infection strategies ofFrontiers in immunology · 2023Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Bacterial pore-forming toxins.Microbiology (Reading, England) · 2022Article
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- The Yin and Yang of Pneumolysin During Pneumococcal Infection.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Cholesterol-dependent cytolysins (CDCs) are essential virulence factors for many human pathogens like Streptococcus pneumoniae (pneumolysin, PLY), Streptococcus pyogenes (streptolysin O, SLO), and Listeria monocytogenes (Listeriolysin, LLO) and induce cytolysis and inflammation. Recently, we identified that pneumococcal PLY interacts with the mannose receptor (MRC-1) on specific immune cells thereby evoking an anti-inflammatory response at sublytic doses. Here, we identified the interaction sites between MRC-1 and CDCs using computational docking. We designed peptides from the CTLD4 domain of MRC-1 that binds to PLY, SLO, and LLO, respectively. In vitro, the peptides blocked CDC-induced cytolysis and inflammatory cytokine production by human macrophages. Also, they reduced PLY-induced damage of the epithelial barrier integrity as well as blocked bacterial invasion into the epithelium in a 3D lung tissue model. Pre-treatment of human DCs with peptides blocked bacterial uptake via MRC-1 and reduced intracellular bacterial survival by targeting bacteria to autophagosomes. In order to use the peptides for treatment in vivo, we developed calcium phosphate nanoparticles (CaP NPs) as peptide nanocarriers for intranasal delivery of peptides and enhanced bioactivity. Co-administration of peptide-loaded CaP NPs during infection improved survival and bacterial clearance in both zebrafish and mice models of pneumococcal infection. We suggest that MRC-1 peptides can be employed as adjunctive therapeutics with antibiotics to treat bacterial infections by countering the action of CDCs.
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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.