ArticlemAbs2016
Context matters: The importance of dimerization-induced conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of neutralizing antibodies.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed, 48 citations in OpenAlex.
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- Integrated immunodominant epitope discovery for dual-purpose rapid and economical diagnostic and immunoprotective applications against MRSA.Frontiers in immunology · 2025Article
- Anti-bacterial monoclonal antibodies: next generation therapy against superbugs.Applied microbiology and biotechnology · 2022Review
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- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
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- Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors.iScience · 2022Article
- Hyperimmune Targeting Staphylococcal Toxins Effectively Protect Against USA 300 MRSA Infection in Mouse Bacteremia and Pneumonia Models.Frontiers in immunology · 2022Article
- Development of Combination Vaccine Conferring Optimal Protection against Six Pore-Forming Toxins of Staphylococcus aureus.Infection and immunity · 2021Article
- Genetic variation of staphylococcal LukAB toxin determines receptor tropism.Nature microbiology · 2021Article
- IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus.Immunity · 2020Article
- Review
- Unbiased Identification of Immunogenic Staphylococcus aureus Leukotoxin B-Cell Epitopes.Infection and immunity · 2020Article
- Genome Sequence of a Highly VirulentCurrent genomics · 2020Article
- Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Rational Design of Toxoid Vaccine Candidates forToxins · 2019Article
- Fighting Staphylococcus aureus Biofilms with Monoclonal Antibodies.Trends in microbiology · 2019Review
- Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LukGH (LukAB) is a potent leukocidin of Staphylococcus aureus that lyses human phagocytic cells and is thought to contribute to immune evasion. Unlike the other bi-component leukocidins of S. aureus, LukGH forms a heterodimer before binding to its receptor, CD11b expressed on professional phagocytic cells, and displays significant sequence variation. We employed a high diversity human IgG1 library presented on yeast cells to discover monoclonal antibodies (mAbs) neutralizing the cytolytic activity of LukGH. Recombinant LukG and LukH monomers or a LukGH dimer were used as capture antigens in the library selections. We found that mAbs identified with LukG or LukH as bait had no or very low toxin neutralization potency. In contrast, LukGH dimer-selected antibodies proved to be highly potent, and several mAbs were able to neutralize even the most divergent LukGH variants. Based on biolayer interferometry and mesoscale discovery, the high affinity antibody binding site on the LukGH complex was absent on the individual monomers, suggesting that it was generated upon formation of the LukG-LukH dimer. X-ray crystallography analysis of the complex between the LukGH dimer and the antigen-binding fragment of a very potent mAb (PDB code 5K59) indicated that the epitope is located in the predicted cell binding region (rim domain) of LukGH. The corresponding IgG inhibited the binding of LukGH dimer to target cells. Our data suggest that knowledge of the native conformation of target molecules is essential to generate high affinity and functional mAbs.
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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.