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.

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.

Coassociation between Group B Streptococcus and Candida albicans Promotes Interactions with Vaginal Epithelium.

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia, and meningitis worldwide. In the majority of cases, GBS is transmitted vertically from mother to neonate, making maternal vaginal colonization a key risk factor for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of the female genitourinary tract and the causative agent of vaginal thrush. Carriage of C. albicans has been shown to be an independent risk factor for vaginal colonization by GBS. However, the nature of interactions between these two microbes is poorly understood. This study provides evidence of a reciprocal, synergistic interplay between GBS and C. albicans that may serve to promote their cocolonization of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515 (serotype Ia) are shown to physically interact with C. albicans, with the bacteria exhibiting tropism for candidal hyphal filaments. This interaction enhances association levels of both microbes with the vaginal epithelial cell line VK2/E6E7. The ability of GBS to coassociate with C. albicans is dependent upon expression of the hypha-specific adhesin Als3. In turn, expression of GBS antigen I/II family adhesins (Bsp polypeptides) facilitates this coassociation and confers upon surrogate Lactococcus lactis the capacity to exhibit enhanced interactions with C. albicans on vaginal epithelium. As genitourinary tract colonization is an essential first step in the pathogenesis of GBS and C. albicans, the coassociation mechanism reported here may have important implications for the risk of disease involving both of these pathogens.

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae.

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans Complementary crystallographic and biophysical characterization of BspA reveal a novel ß-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections.

Well-being and academic achievement in secondary school pupils: The unique effects of burnout and engagement.

The main goal of this study was to examine the relationship among burnout, engagement, well-being, and academic performance in Portuguese secondary school pupils. The existence of gender related differences in these relationships was also investigated. The sample was composed of 489 pupils who attended an academic track at secondary school. Results of multi-group structural equation modelling indicated that higher levels of cynicism towards studies were associated with lower academic achievement. Exhaustion was not uniquely related to the adolescents' academic achievement or well-being. However, higher levels of engagement, namely dedication and vigour, were related to higher levels of well-being. Moreover, vigour was also uniquely associated with academic achievement. The results were similar for boys and girls. Implications for intervention and future research are discussed.