title: Resistance of Neisseria meningitidis to human serum depends on T and B cell stimulating protein B.
abstract: The ability of the human bacterial pathogen Neisseria meningitidis to cause invasive disease depends on survival in the bloodstream via mechanisms to suppress complement activation. In this study, we show that prophage genes coding for T and B cell stimulating protein B (TspB), which is an immunoglobulin-binding protein, are essential for survival of N. meningitidis group B strain H44/76 in normal human serum (NHS). H44/76 carries three genes coding for TspB. Mutants having all tspB genes inactivated did not survive in >5% NHS or IgG-depleted NHS. TspB appeared to inhibit IgM-mediated activation of the classical complement pathway, since survival of the tspB triple knockout was the same as that of the parent strain or a complemented mutant when the classical pathway was inactivated by depleting NHS of C1q and was increased in IgM-depleted NHS. A mutant solely carrying tspB gene nmbh4476_0681 was as resistant as the parent strain, while mutants carrying only nmbh4476_0598 or nmbh4476_1698 were killed in ≥5% NHS. The phenotype associated with TspB is formation of a matrix containing TspB, IgG, and DNA that envelopes aggregates of bacteria. Recombinant proteins corresponding to particular subdomains of TspB were found to have human IgG Fcγ- and/or DNA-binding activity, but only TspB derivatives containing both domains formed large, biofilm-like aggregates when combined with purified IgG and DNA. Recognizing the role of TspB in serum resistance may lead to a better understanding of why strains that carry tspB genes are associated with invasive meningococcal disease.
authors.affiliation: UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Maike G
authors.initials: MG
authors.lastname: Müller
authors.affiliation: UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Nina E
authors.initials: NE
authors.lastname: Moe
authors.affiliation: UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Phillip Q
authors.initials: PQ
authors.lastname: Richards
authors.affiliation: UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA gmoe@chori.org.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Moe
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics*; D018441:Biofilms; D001770:Blood Bactericidal Activity / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology; D003171:Complement Pathway, Classical / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008589:Meningococcal Infections / Q000276:immunology / Q000473:pathology; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D017452:Receptors, IgG; D015922:Complement C1q