ArticlePLoS pathogens2013
Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Complement-mediated opsonization of invasive group A Streptococcus pyogenes strain AP53 is regulated by the bacterial two-component cluster of virulence responder/sensor (CovRS) system.The Journal of biological chemistry · 2013Trial
- Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A.Communications biology · 2026Article
- The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies.EMBO molecular medicine · 2026Article
- Group A Streptococcal Virulence Factors and Vaccine Development-An Update.Microorganisms · 2026Review
- Group A Streptococcus interacts with glycosaminoglycans via M proteins to modulate bacterial adherence in vitro.The FEBS journal · 2025Article
- C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells.Journal of innate immunity · 2024Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- Insertion of an immunodominant T helper cell epitope within the Group AFrontiers in immunology · 2023Article
- Group BJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- Hijacking Factor H for Complement Immune Evasion.Frontiers in immunology · 2021Review
- Subdominance in Antibody Responses: Implications for Vaccine Development.Microbiology and molecular biology reviews : MMBR · 2020Review
- A Role of Epithelial Cells and Virulence Factors in Biofilm Formation by Streptococcus pyogenesInfection and immunity · 2020Article
- Solution structural model of the complex of the binding regions of human plasminogen with its M-protein receptor from Streptococcus pyogenes.Journal of structural biology · 2019Article
- Surface Proteins on Gram-Positive Bacteria.Microbiology spectrum · 2019Review
- Toxins and Superantigens of Group A Streptococci.Microbiology spectrum · 2019Article
- Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization.Journal of structural biology · 2018Article
- Variation, Indispensability, and Masking in the M protein.Trends in microbiology · 2018Review
- Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial PathogenJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Incremental Contributions of FbaA and Other Impetigo-Associated Surface Proteins to Fitness and Virulence of a Classical Group A Streptococcal Skin Strain.Infection and immunity · 2017Article
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.
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