The mechanisms by which Streptococcus pneumoniae penetrates the blood-brain barrier (BBB), reach the CNS and causes meningitis are not fully understood. Adhesion of bacterial cells on the brain microvascular endothelial cells (BMECs), mediated through protein-protein interactions, is one of the crucial steps in translocation of bacteria across BBB. In this work, we proposed a systematic workflow for identification of cell wall associated ligands of pneumococcus that might adhere to the human BMECs. The proteome of S. pneumoniae was biotinylated and incubated with BMECs. Interacting proteins were recovered by affinity purification and identified by data independent acquisition (DIA). A total of 44 proteins were identified from which 22 were found to be surface-exposed. Based on the subcellular location, ontology, protein interactive analysis and literature review, five ligands (adhesion lipoprotein, endo-β-N-acetylglucosaminidase, PhtA and two hypothetical proteins, Spr0777 and Spr1730) were selected to validate experimentally (ELISA and immunocytochemistry) the ligand-BMECs interaction. In this study, we proposed a high-throughput approach to generate a dataset of plausible bacterial ligands followed by systematic bioinformatics pipeline to categorize the protein candidates for experimental validation. The approach proposed here could contribute in the fast and reliable screening of ligands that interact with host cells.
Streptococcus pneumoniae invades the CNS and triggers a strong cellular response. To date, signaling events that occur in the human brain microvascular endothelial cells (hBMECs), in response to pneumococci or its surface adhesins are not mapped comprehensively. We evaluated the response of hBMECs to the adhesion lipoprotein (a laminin binding protein—Lbp) or live pneumococci. Lbp is a surface adhesin recently identified as a potential ligand, which binds to the hBMECs. Transcriptomic analysis was performed by RNA-seq of three independent biological replicates and validated with qRT-PCR using 11 genes. In total 350 differentially expressed genes (DEGs) were identified after infection with S. pneumoniae, whereas 443 DEGs when challenged with Lbp. Total 231 DEGs were common in both treatments. Integrative functional analysis revealed participation of DEGs in cytokine, chemokine, TNF signaling pathways and phagosome formation. Moreover, Lbp induced cell senescence and breakdown, and remodeling of ECM. This is the first report which maps complete picture of cell signaling events in the hBMECs triggered against S. pneumoniae and Lbp. The data obtained here could contribute in a better understanding of the invasion of pneumococci across BBB and underscores role of Lbp adhesin in evoking the gene expression in neurovascular unit.
One of the eternal influencing factors on the development of people´s place of living is the problem of burying. These problems change in time but consequentially require long-term planning, the reservation of an area in a proper territorial community with all planned consequences thoroughly thought through. Cemeteries come close to the course of life in society and its relationship to the values of previous generations. According to the state of the cemetery and its tidiness it is possible to make a judgement on the cultural advancement of society. The loss of rituals and the encroaching secularization of society are connected to making the problems of burials and burying taboo. The objective of this work is an attempt to change this state by leading a discussion on the tradition of burying as part of life in the European context of selected cemeteries in Vienna, Brno and Prague. There are taken into consideration the historical influences and the reasons of introducing legal arrangements, historical connections, urban establishments, funereal arts, architecture and pictures of the cemeteries that were studied. There are observed the present trends in burying and the arrangement of existing cemeteries and comparing them with inter-European influences. The problems of cemeteries are presented with their projection into the future on the cultural and ethical level of the moral code.
Bacterial meningitis is a devastating worldwide disease. Half of the survivors of meningitis remain with permanent neurological sequelae. The pathogenesis of meningitis is based on a complex host-pathogen interaction. Streptococcus pneumoniae is a life-threatening neuroinvasive pathogen that asymptomatically colonizes the upper respiratory tract. Adherence of pneumococci to the host epithelium is a prerequisite in the onset of streptococcal infections; such adherence is favored by the formation of bacterial pili. In this article, we will describe the pneumococcal pili and its contribution to the onset of meningitis.
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