The Group B Streptococcal surface antigen I/II protein, BspC, interacts with host vimentin to promote adherence to brain endothelium and inflammation during the pathogenesis of meningitis

Liwen Deng, Brady L Spencer, Joshua A Holmes, Rong Mu, Sara Rego, Thomas A Weston, Yoonsung Hu, Glenda F Sanches, Sunghyun Yoon, Nogi Park, Prescilla E Nagao, Howard F Jenkinson, Justin A Thornton, Keun Seok Seo, Angela H Nobbs, Kelly S Doran

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Abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) normally colonizes healthy adults but can cause invasive disease, such as meningitis, in the newborn. To gain access to the central nervous system, GBS must interact with and penetrate brain or meningeal blood vessels; however, the exact mechanisms are still being elucidated. Here, we investigate the contribution of BspC, an antigen I/II family adhesin, to the pathogenesis of GBS meningitis. Disruption of the bspC gene reduced GBS adherence to human cerebral microvascular endothelial cells (hCMEC), while heterologous expression of BspC in non-adherent Lactococcus lactis conferred bacterial attachment. In a murine model of hematogenous meningitis, mice infected with ΔbspC mutants exhibited lower mortality as well as decreased brain bacterial counts and inflammatory infiltrate compared to mice infected with WT GBS strains. Further, BspC was both necessary and sufficient to induce neutrophil chemokine expression. We determined that BspC interacts with the host cytoskeleton component vimentin, and confirmed this interaction using a bacterial two-hybrid assay, microscale thermophoresis, immunofluorescent staining, and imaging flow cytometry. Vimentin null mice were protected from WT GBS infection and also exhibited less inflammatory cytokine production in brain tissue. These results suggest that BspC and the vimentin interaction is critical for the pathogenesis of GBS meningitis.

Original languageEnglish
Article numbere1007848
Number of pages30
JournalPLoS Pathogens
Volume15
Issue number6
DOIs
Publication statusPublished - 10 Jun 2019

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    Deng, L., Spencer, B. L., Holmes, J. A., Mu, R., Rego, S., Weston, T. A., Hu, Y., Sanches, G. F., Yoon, S., Park, N., Nagao, P. E., Jenkinson, H. F., Thornton, J. A., Seo, K. S., Nobbs, A. H., & Doran, K. S. (2019). The Group B Streptococcal surface antigen I/II protein, BspC, interacts with host vimentin to promote adherence to brain endothelium and inflammation during the pathogenesis of meningitis. PLoS Pathogens, 15(6), [e1007848]. https://doi.org/10.1371/journal.ppat.1007848