Staphylococcus aureus expresses a cell surface protein that binds both IgG and β2-glycoprotein I

Zhang, Lihong; Jacobsson, Karin; Ström, Katrin; Lindberg, Martin; Frykberg, Lars

doi:10.1099/13500872-145-1-177

Cited by 54 publications

(43 citation statements)

References 25 publications

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“…(1 and 2) are homologous to the IgBDs of SpA (48). Domains 3 and 4 associate with complement components C3 and factor H, and the C-terminal domain has been proposed to retain some secreted Sbi molecules in the staphylococcal envelope by binding to lipoteichoic acids (6,44).…”

Section: Resultsmentioning

confidence: 99%

Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice

et al. 2012

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ABSTRACTStaphylococcus aureusis a leading cause of human soft tissue infections and bacterial sepsis. The emergence of antibiotic-resistant strains (methicillin-resistantS. aureus[MRSA]) has prompted research into staphylococcal vaccines and preventive measures. The envelope ofS. aureusis decorated with staphylococcal protein A (SpA), which captures the Fcγ portion of immunoglobulins to prevent opsonophagocytosis and associates with the Fab portion of VH3-type B cell receptors to trigger B cell superantigen activity. Nontoxigenic protein A (SpAKKAA), when used as an immunogen in mice, stimulates humoral immune responses that neutralize the Fcγ and the VH3+Fab binding activities of SpA and provide protection from staphylococcal abscess formation in mice. Here, we isolated monoclonal antibodies (MAbs) against SpAKKAAthat, by binding to the triple-helical bundle fold of its immunoglobulin binding domains (IgBDs), neutralize the Fcγ and Fab binding activities of SpA. SpAKKAAMAbs promoted opsonophagocytic killing of MRSA in mouse and human blood, provided protection from abscess formation, and stimulated pathogen-specific immune responses in a mouse model of staphylococcal disease. Thus, SpAKKAAMAbs may be useful for the prevention and therapy of staphylococcal disease in humans.

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Section: Resultsmentioning

confidence: 99%

Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice

et al. 2012

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“…Although the incidence and clinical significance of β2GPI-dependent aCL Ab's and anti-β2GPI Ab's in infectious diseases remains largely unknown, it is possible that infections might trigger the development of pathogenic anti-β2GPI Ab's, conceivably by molecular mimicry, and thus promote the development of APS, particularly in predisposed individuals. Recently, employing the shotgun phage display technique, Zhang et al (34) identified a Staphylococcus aureus protein, Sbi, which binds β2GPI and serves as target molecule for IgG binding. It was also shown that protein Sbi, and thus the β2GPI-binding potential, is expressed on the staphylococcal cell surface at levels varying between strains (34).…”

Section: Discussionmentioning

confidence: 99%

Bacterial induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome

Blank¹,

Krause²,

Fridkin³

et al. 2002

J. Clin. Invest.

258

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The antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against β2-glycoprotein-I (β2GPI). The factors causing production of anti-β2GPI remain unidentified, but an association with infectious agents has been reported. Recently, we identified a hexapeptide (TLRVYK) that is recognized specifically by a pathogenic anti-β2GPI mAb. In the present study we evaluated the APS-related pathogenic potential of microbial pathogens carrying sequences related to this hexapeptide. Mice immunized with a panel of microbial preparations were studied for the development of anti-β2GPI autoantibodies. IgG specific to the TLRVYK peptide were affinity purified from the immunized mice and passively infused intravenously into naive mice at day 0 of pregnancy. APS parameters were evaluated in the infused mice on day 15 of pregnancy. Following immunization, high titers of antipeptide [TLRVYK] anti-β2GPI Ab's were observed in mice immunized with Haemophilus influenzae, Neisseria gonorrhoeae, or tetanus toxoid. The specificity of binding to the corresponding target molecules was confirmed by competition and immunoblot assays. Naive mice infused with the affinity-purified antipeptide Ab's had significant thrombocytopenia, prolonged activated partial thromboplastin time and elevated percentage of fetal loss, similar to a control group of mice immunized with a pathogenic anti-β2GPI mAb. Our study establishes a mechanism of molecular mimicry in experimental APS, demonstrating that bacterial peptides homologous with β2GPI induce pathogenic anti-β2GPI Ab's along with APS manifestations.

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“…Phage display studies of S. aureus strain 8325-4 genomic DNA revealed a novel Ig-binding peptide that was later found to be part of Sbi (second binding protein of immunoglobulin) (46,47). At its N terminus are two IgG-binding domains (D1 and D2 [D1D2]) with sequence similarity to the IgG-binding domains of Spa (Fig.…”

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confidence: 99%

The Sbi Protein Is a Multifunctional Immune Evasion Factor of Staphylococcus aureus

et al. 2011

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The second immunoglobulin-binding protein (Sbi) of Staphylococcus aureus has two N-terminal domains that bind the Fc region of IgG in a fashion similar to that of protein A and two domains that can bind to the complement protein C3 and promote its futile consumption in the fluid phase. It has been proposed that Sbi helps bacteria to avoid innate immune defenses. By comparing a mutant defective in Sbi with mutants defective in protein A, clumping factor A, iron-regulated surface determinant H, and capsular polysaccharide, it was shown that Sbi is indeed an immune evasion factor that promotes bacterial survival in whole human blood and the avoidance of neutrophil-mediated opsonophagocytosis. Sbi is present in the culture supernatant and is also associated with the cell envelope. S. aureus strains that expressed truncates of Sbi lacking N-terminal domains D1 and D2 (D1D2) or D3 and D4 (D3D4) or a C-terminal truncate that was no longer retained in the cell envelope were analyzed. Both the secreted and envelope-associated forms of Sbi contributed to immune evasion. The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active.

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Staphylococcus aureus expresses a cell surface protein that binds both IgG and β2-glycoprotein I

Cited by 54 publications

References 25 publications

Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice

Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice

Bacterial induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome

The Sbi Protein Is a Multifunctional Immune Evasion Factor of Staphylococcus aureus

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