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. Group B Streptococcus (GBS) typically colonizes healthy adults but can cause severe disease in immune compromised individuals, including newborns. Despite wide-spread intrapartum antibiotic prophylaxis given to pregnant women, GBS remains a leading cause of neonatal meningitis. To cause meningitis, GBS must interact with and penetrate the blood-brain barrier (BBB), which separates bacteria and immune cells in the blood from the brain. In order to develop targeted therapies to treat GBS meningitis, it is important to understand the mechanisms of BBB crossing. Here, we describe the role of the GBS surface factor, BspC, in promoting meningitis and discover the host ligand for BspC, vimentin, which is an intermediate filament protein that is constitutively expressed by endothelial cells. We determined that BspC interacts with the C-terminal domain of cell-surface vimentin to promote bacterial attachment to brain endothelial cells and that purified BspC protein can induce immune signaling pathways. In a mouse model of hematogenous meningitis, we observed that a GBS mutant lacking BspC was less virulent compared to WT GBS and resulted in less inflammatory disease. We also observed that mice lacking vimentin were protected from GBS infection. These results reveal the importance of the BspC-vimentin interaction in the progression of GBS meningitis disease.

O artigo revisa a literatura sobre a emergência de infecções humanas causadas por Corynebacterium ulcerans em diversos países, incluindo o Brasil. Foi realizada análise de artigos publicados entre 1926 e 2011 nas bases Medline/PubMed e SciELO, bem como artigos e informes do Ministério da Saúde. Apresenta-se um esquema de triagem, rápido, econômico e de fácil execução, capaz de permitir a realização do diagnóstico presuntivo de C. ulcerans e C. diphtheriae na maioria dos laboratórios brasileiros públicos e privados. A circulação de C. ulcerans em vários países, aliada aos recentes casos de isolamento do patógeno no Rio de Janeiro, é um alerta a clínicos, veterinários e microbiologistas sobre a ocorrência de difteria zoonótica e a circulação do C. ulcerans em regiões urbanas e rurais do território nacional e/ou da América Latina.

The genus Streptococcus comprises important pathogens, many of them are part of the human or animal microbiota. Advances in molecular genetics, taxonomic approaches and phylogenomic studies have led to the establishment of at least 100 species, that have a severe impact on human health and are responsible for substantial economic losses to agriculture. The infectivity of the pathogens is linked to cell‐surface components and/or secreted virulence factors. Bacteria have evolved sophisticated and multifaceted adaptation strategies to the host environment, including biofilm formation, survival within professional phagocytes, escape the host immune response, amongst others. This review focuses on virulence mechanism and zoonotic potential of Streptococcus species from pyogenic (S. agalactiae, S. pyogenes) and mitis groups (S. pneumoniae).

Corynebacterium diphtheriae still represents a global medical challenge, particularly due to the significant number of individuals susceptible to diphtheria and the emergence of non-toxigenic strains as the causative agents of invasive infections. In this study, we characterized the clinical and microbiological features of what we believe to be the first case of C. diphtheriae infection of a percutaneous nephrostomy catheter insertion site in an elderly patient with a fatal bladder cancer. Moreover, we demonstrated the potential role of adherence, biofilm formation and fibrin deposition traits in C. diphtheriae from the catheter-related infection. Non-toxigenic C. diphtheriae isolated from the purulent discharge (named strain BR-CAT5003748) was identified by the API Coryne system (code 1 010 324) and a multiplex PCR for detection of dtxR and tox genes. Strain BR-CAT5003748 showed resistance to oxacillin, ceftazidime and ciprofloxacin. In experiments performed in vitro, the catheter isolate was classified as moderately hydrophobic and as moderately adherent to polystyrene surfaces. Glass provided a more effective surface for biofilm formation than polystyrene. Micro-organisms adhered to (>1.5×10⁶ c.f.u.) and multiplied on surfaces of polyurethane catheters. Microcolony formation (a hallmark of biofilm formation) and amorphous accretions were observed by scanning electron microscopy on both external and luminal catheter surfaces. Micro-organisms yielded simultaneous expression of localized adherence-like and aggregative-like (LAL/AAL) adherence patterns to HEp-2 cells. Interestingly, the coagulase tube test resulted in the formation of a thin layer of fibrin embedded in rabbit plasma by the non-toxigenic BR-CAT5003748 strain. In conclusion, C. diphtheriae should be recognized as a potential cause of catheter-related infections in at-risk populations such as elderly and cancer patients. LAL/AAL strains may be associated with virulence traits that enable C. diphtheriae to effectively produce biofilms on catheter surfaces. Biofilm formation and fibrin deposition could have contributed to the persistence of C. diphtheriae at the infected insertion site and the obstruction of the nephrostomy catheter.

Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.