Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

Karita Haapasalo, Hanna Jarva, Tuula Siljander, Wezenet Tewodros, Jaana Vuopio-Varkila, T. Sakari Jokiranta

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.
    Originalspråkengelska
    TidskriftMolecular Microbiology
    Volym70
    Utgåva3
    Sidor (från-till)583-594
    Antal sidor12
    ISSN0950-382X
    DOI
    StatusPublicerad - 2008
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Vetenskapsgrenar

    • 3111 Biomedicinska vetenskaper

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    @article{95b677f0fc344c3d89567d587c7cba44,
    title = "Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes",
    abstract = "The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.",
    keywords = "HEMOLYTIC-UREMIC SYNDROME, HEPARIN-BINDING DOMAIN, SHORT CONSENSUS REPEAT, GROUP-A STREPTOCOCCI, C-REACTIVE PROTEIN, RCA GENE-CLUSTER, MACULAR DEGENERATION, ALTERNATIVE PATHWAY, C3B/C4B RECEPTOR, SURFACE PROTEIN, 3111 Biomedicine",
    author = "Karita Haapasalo and Hanna Jarva and Tuula Siljander and Wezenet Tewodros and Jaana Vuopio-Varkila and Jokiranta, {T. Sakari}",
    note = "This article has an erratum:Doi 10.1111/j.1365-2958.2012.07991.x Volume: Proceeding volume:",
    year = "2008",
    doi = "10.1111/j.1365-2958.2008.06347.x",
    language = "English",
    volume = "70",
    pages = "583--594",
    journal = "Molecular Microbiology",
    issn = "0950-382X",
    publisher = "Wiley",
    number = "3",

    }

    Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes. / Haapasalo, Karita; Jarva, Hanna; Siljander, Tuula; Tewodros, Wezenet; Vuopio-Varkila, Jaana; Jokiranta, T. Sakari.

    I: Molecular Microbiology, Vol. 70, Nr. 3, 2008, s. 583-594.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

    AU - Haapasalo, Karita

    AU - Jarva, Hanna

    AU - Siljander, Tuula

    AU - Tewodros, Wezenet

    AU - Vuopio-Varkila, Jaana

    AU - Jokiranta, T. Sakari

    N1 - This article has an erratum:Doi 10.1111/j.1365-2958.2012.07991.x Volume: Proceeding volume:

    PY - 2008

    Y1 - 2008

    N2 - The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.

    AB - The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.

    KW - HEMOLYTIC-UREMIC SYNDROME

    KW - HEPARIN-BINDING DOMAIN

    KW - SHORT CONSENSUS REPEAT

    KW - GROUP-A STREPTOCOCCI

    KW - C-REACTIVE PROTEIN

    KW - RCA GENE-CLUSTER

    KW - MACULAR DEGENERATION

    KW - ALTERNATIVE PATHWAY

    KW - C3B/C4B RECEPTOR

    KW - SURFACE PROTEIN

    KW - 3111 Biomedicine

    U2 - 10.1111/j.1365-2958.2008.06347.x

    DO - 10.1111/j.1365-2958.2008.06347.x

    M3 - Article

    VL - 70

    SP - 583

    EP - 594

    JO - Molecular Microbiology

    JF - Molecular Microbiology

    SN - 0950-382X

    IS - 3

    ER -