Dataset Information

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 Fc?- 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.

SUBMITTER: Muller MG

PROVIDER: S-EPMC4363439 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Resistance of Neisseria meningitidis to human serum depends on T and B cell stimulating protein B.

Müller Maike G MG Moe Nina E NE Richards Phillip Q PQ Moe Gregory R GR

Infection and immunity 20150112 4

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 inacti ...[more]

PMID: 25583528

Similar Datasets

Project description:Neisseria meningitidis remains an important cause of septicemia and meningitis. One of its major virulence traits is its ability to avoid killing by human serum. In the present work, the effect of growth phase (exponential versus stationary) and growth medium (THB versus Catlin) on normal human serum (NHS) sensitivity was assessed on two N. meningitidis serogroup B strains (MC58 and M982). Both strains were found to be dramatically more resistant to 20% NHS killing at early exponential phase than at stationary phase (73-100% survival after 1 to 2 hours of growth compared to less than 10% survival after 7 hours of growth). This growth phase effect was detected only when a rich medium (THB) was used while no such effect was observed using Catlin medium. KDO (2-Keto-3-deoxyoctulosonic acid) and sialic acid content were measured on serum-resistant and serum-sensitive bacteria and were found comparable, indicating that differences in LPS and capsule expression were not at the origin of the observed phenotypes. Transcriptome profiling using a PCR-array was used to compare serum-resistant and serum-sensitive bacteria. A set of 255 genes was found to be differentially expressed with 159 genes up-regulated in serum-resistant bacteria, among them 12 genes involved in glucose catabolism and 22 are known virulence factors. Overall, this study shows that serum-resistant phenotype of N. meningitidis could be obtained through modulating growth conditions. The nature of growth media and growth phases have a major impact on the ability of N. meningitidis to resist to NHS killing. Consequently, the present work underlines the critical importance of carefully controlling those parameters in any studies aimed at investigating the mechanisms and factors involved in N. meningitidis serum-resistance. All experiments were performed in dye swap. These experiments were performed with 2 strains of N. meningitidis serogroup B. In one set of experiments, the gene expression profile of bacteria cultured in THB medium during 7h was compared with the corresponding profile of bacteria cultured during 1h in the same medium. In a second set of experiments, the gene expression profile of 1 strain cultured in THB medium during 7h was compared with the corresponding profile of the same strain cultured in Catlin medium during 7h. 3 biological replicates were performed for each comparison.

Dataset Information

Resistance of Neisseria meningitidis to human serum depends on T and B cell stimulating protein B.

Publications

Resistance of Neisseria meningitidis to human serum depends on T and B cell stimulating protein B.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets