Identification of a phage-encoded immunoglobulin-binding protein from invasive Neisseria meningitidis
Immunoglobulin (Ig)-binding proteins are employed by a variety of organisms to evade the immune system. We now report for the first time that meningococcal strains from several capsular groups exhibit Ig-binding activity that is dependent on human serum factors. A protein mediating Ig binding was id...
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Veröffentlicht in: | The Journal of immunology (1950) 2013-08, Vol.191 (6), p.3287-3296 |
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Sprache: | eng |
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Zusammenfassung: | Immunoglobulin (Ig)-binding proteins are employed by a variety of organisms to evade the immune system. We now report for the first time that meningococcal strains from several capsular groups exhibit Ig-binding activity that is dependent on human serum factors. A protein mediating Ig binding was identified as T and B cell stimulating protein B (TspB) by immunoprecipitation and by mass spectroscopic analysis of tryptic peptides. Recombinant TspB and derivatives verified Ig binding, with a preference for human IgG2 Fc, and localized the IgG-binding region to a highly conserved subdomain of TspB. Antiserum produced in mice against the conserved subdomain, detected the presence of TspB on the cell surface by flow cytometry when bacteria were grown in the presence of human serum. By fluorescence microscopy, we observed formation of an extracellular matrix having characteristics of a biofilm containing TspB, human IgG, DNA, and large aggregates of bacteria. TspB is encoded by gene
ORF6
in prophage DNA, which others have shown is associated with invasive meningococcal strains. Knocking out
ORF6
genes eliminated IgG binding and formation of large bacterial aggregates in biofilm. Reintroduction of a wild-type
ORF6
gene by phage transduction restored the phenotype. The results show that TspB mediated IgG binding and aggregate/biofilm formation triggered by factors in human serum. As has been observed for other Ig-binding proteins, the activities mediated by TspB may provide protection against immune responses, which is in accordance with the association of prophage DNA carrying
ORF6
with invasive meningococcal strains. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.1301153 |