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        Surface Glycopolymers Are Crucial for <i>In Vitro</i> Anti-Wall Teichoic Acid IgG-Mediated Complement Activation and Opsonophagocytosis of <i>Staphylococcus aureus</i>

        Lee, Jong-Ho,Kim, Na-Hyang,Winstel, Volker,Kurokawa, Kenji,Larsen, Jesper,An, Jang-Hyun,Khan, Adnan,Seong, Min-Young,Lee, Min Ja,Andersen, Paal Skytt,Peschel, Andreas,Lee, Bok Luel American Society for Microbiology 2015 Infection and immunity Vol.83 No.11

        <P>The cell envelopes of many Gram-positive bacteria contain wall teichoic acids (WTAs). <I>Staphylococcus aureus</I> WTAs are composed of ribitol phosphate (RboP) or glycerol phosphate (GroP) backbones substituted with <SMALL>d</SMALL>-alanine and <I>N</I>-acetyl-<SMALL>d</SMALL>-glucosamine (GlcNAc) or <I>N</I>-acetyl-<SMALL>d</SMALL>-galactosamine (GalNAc). Two WTA glycosyltransferases, TarM and TarS, are responsible for modifying the RboP WTA with α-GlcNAc and β-GlcNAc, respectively. We recently reported that purified human serum anti-WTA IgG specifically recognizes β-GlcNAc of the staphylococcal RboP WTA and then facilitates complement C3 deposition and opsonophagocytosis of <I>S. aureus</I> laboratory strains. This prompted us to examine whether anti-WTA IgG can induce C3 deposition on a diverse set of clinical <I>S. aureus</I> isolates. To this end, we compared anti-WTA IgG-mediated C3 deposition and opsonophagocytosis abilities using 13 different staphylococcal strains. Of note, the majority of <I>S. aureus</I> strains tested was recognized by anti-WTA IgG, resulting in C3 deposition and opsonophagocytosis. A minority of strains was not recognized by anti-WTA IgG, which correlated with either extensive capsule production or an alteration in the WTA glycosylation pattern. Our results demonstrate that the presence of WTAs with TarS-mediated glycosylation with β-GlcNAc in clinically isolated <I>S. aureus</I> strains is an important factor for induction of anti-WTA IgG-mediated C3 deposition and opsonophagocytosis.</P>

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        Glycoepitopes of Staphylococcal Wall Teichoic Acid Govern Complement-mediated Opsonophagocytosis via Human Serum Antibody and Mannose-binding Lectin

        Kurokawa, Kenji,Jung, Dong-Jun,An, Jang-Hyun,Fuchs, Katharina,Jeon, Yu-Jin,Kim, Na-Hyang,Li, Xuehua,Tateishi, Koichiro,Park, Ji Ae,Xia, Guoqing,Matsushita, Misao,Takahashi, Kazue,Park, Hee-Ju,Peschel, American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.43

        <P>Serum antibodies and mannose-binding lectin (MBL) are important host defense factors for host adaptive and innate immunity, respectively. Antibodies and MBL also initiate the classical and lectin complement pathways, respectively, leading to opsonophagocytosis. We have shown previously that <I>Staphylococcus aureus</I> wall teichoic acid (WTA), a cell wall glycopolymer consisting of ribitol phosphate substituted with α- or β-<I>O-N</I>-acetyl-<SMALL>d</SMALL>-glucosamine (GlcNAc) and <SMALL>d</SMALL>-alanine, is recognized by MBL and serum anti-WTA IgG. However, the exact antigenic determinants to which anti-WTA antibodies or MBL bind have not been determined. To answer this question, several <I>S. aureus</I> mutants, such as α-GlcNAc glycosyltransferase-deficient <I>S. aureus</I> Δ<I>tarM</I>, β-GlcNAc glycosyltransferase-deficient Δ<I>tarS</I>, and Δ<I>tarMS</I> double mutant cells, were prepared from a laboratory and a community-associated methicillin-resistant <I>S. aureus</I> strain. Here, we describe the unexpected finding that β-GlcNAc WTA-deficient Δ<I>tarS</I> mutant cells (which have intact α-GlcNAc) escape from anti-WTA antibody-mediated opsonophagocytosis, whereas α-GlcNAc WTA-deficient Δ<I>tarM</I> mutant cells (which have intact β-GlcNAc) are efficiently engulfed by human leukocytes via anti-WTA IgG. Likewise, MBL binding in <I>S. aureus</I> cells was lost in the Δ<I>tarMS</I> double mutant but not in either single mutant. When we determined the serum concentrations of the anti-α- or anti-β-GlcNAc-specific WTA IgGs, anti-β-GlcNAc WTA-IgG was dominant in pooled human IgG fractions and in the intact sera of healthy adults and infants. These data demonstrate the importance of the WTA sugar conformation for human innate and adaptive immunity against <I>S. aureus</I> infection.</P>

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