Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with high case fatality rate despite treatment antibiotics. Pneumococci meningitis by invading blood and penetrating blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy brain biopsies from patients who died pneumococcal we observe that pneumococci colocalize two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) platelet cell adhesion...

ABSTRACT Gram-positive bacteria, including the major respiratory pathogen Streptococcus pneumoniae , were recently shown to produce extracellular vesicles (EVs) that likely originate from plasma membrane and are released into environment. EVs may function as cargo for many bacterial proteins, however, their involvement in cellular processes interactions with innate immune system poorly understood. Here, pneumococci characterized immunomodulatory effects investigated. Pneumococcal protruding...

Importance Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective To describe risks following diagnosis Sweden. Design, Setting, Participants This retrospective registry-based cohort study included individuals diagnosed (younger than 18 years) general population controls matched (1:9) by age, sex, place residence. Data were retrieved from Swedish National Patient Register...

Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium and the predominant cause of bacterial meningitis. Meningitis thought to occur as result pneumococci crossing blood-brain barrier invade Central Nervous System (CNS); yet little known about steps preceding immediate disease development. To study interactions between vascular endothelium prior meningitis we used an established bacteremia-derived model in combination with immunofluorescent imaging. Brain tissue mice...

Bacterial meningitis is an inflammation of the meninges which covers and protects brain spinal cord. Such mostly caused by blood-borne bacteria that cross blood-brain barrier (BBB) finally invade parenchyma. Pathogens such as Streptococcus pneumoniae , Neisseria meningitidis Haemophilus influenzae are main etiological causes bacterial meningitis. After trafficking across BBB, pathogens in interact with neurons, fundamental units Central Nervous System, other types glial cells. Although...

Streptococcus pneumoniae (pneumococcus) is the primary cause of bacterial meningitis. Pneumococcal bacteria penetrates blood-brain barrier (BBB), but factors that enable this process are not known. Here, we determined expression pneumococcal pilus-1, which includes pilus adhesin RrgA, promotes penetration through BBB in a mouse model. S. colonized respiratory epithelium and grew bloodstream were chains variable lengths; however, pneumococci entered brain division-competent, spherical, single...

Streptococcus pneumoniae, the pneumococcus, is a cause of major illness globally. Invasive pneumococcal disease (IPD) characterized by pneumococci invading blood (bacteremia), lungs (pneumonia), or brain and cerebrospinal fluid (meningitis). Meningitis remains an important global health concern because half survivors experience long-term neurological damage. The antibiotics commonly used to treat infections are β-lactams macrolides, however, S. pneumoniae nowadays often resistant one several...

The Gram-positive bacterium Streptococcus pneumoniae is the main causative agent of bacterial meningitis. S. thought to invade central nervous system via bloodstream by crossing vascular endothelium blood-brain barrier. exact mechanism which pneumococci cross endothelial cell barriers before meningitis develops unknown. Here, we investigated role PECAM-1/CD31, one major adhesion molecules, in Mice were intravenously infected with and sacrificed at various time points represent stages...

Microglia have a pivotal role in the pathophysiology of bacterial meningitis. The goal this review is to provide an overview on how microglia respond pathogens targeting brain, interplay between and bacteria can be studied experimentally, possible ways use gained knowledge identify novel preventive therapeutic strategies. We discuss dual disease development, beneficial functions crucial for clearing, destructive properties through triggering neuroinflammation, characterized by cytokine...

Neuronal damage is a major consequence of bacterial meningitis, but little known about mechanisms interaction with neurons leading to neuronal cell death. Streptococcus pneumoniae (pneumococcus) cause meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due damage. Here, we studied for pneumococcal interactions neurons. Using human primary neurons, pull-down experiments mass spectrometry, show that pneumococci interact cytoskeleton...

Pneumococcal meningitis, inflammation of the meninges due to an infection Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is most common form community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate solute transport glymphatic system, facilitating exchange compounds between brain parenchyma and cerebrospinal fluid (CSF), which important for clearance waste away from brain. Wistar rats, subjected either...

Article28 September 2020Open Access Source DataTransparent process Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation development of pneumococcal disease Karthik Subramanian orcid.org/0000-0002-4381-5037 Department Microbiology, Tumor Cell Biology, Karolinska Institutet, Stockholm, Sweden Search for more papers by this author Federico Iovino Vasiliki Tsikourkitoudi orcid.org/0000-0003-0820-3585 Padryk Merkl Sultan Ahmed Laboratory Medicine, Huddinge,...

Streptococcus pneumoniae is one of the major causative agents pneumonia, sepsis, meningitis and other morbidities. In spite its heavy disease burden, surprisingly little known about mechanisms involved in switch life style, from commensal colonizer nasopharynx to invasive pathogen. vitro experiments, mouse models have shown that S. can be internalized by host cells, which coupled with intracellular vesicle transport through i.e. transcytosis, suggested first step disease. To further dissect...

Streptococcus pneumoniae is thought to adhere the blood-brain barrier (BBB) endothelium prior causing meningitis. The platelet activating factor receptor (PAFR) has been implicated in this adhesion but there a paucity of data demonstrating direct binding bacteria PAFR. Additionally, studies that inhibit PAFR strongly suggest alternative receptors for pneumococci are present on endothelium. Therefore, we studied roles and pIgR, an established epithelial pneumococcal receptor, brain...

Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted replacement of vaccine-type with nonvaccine-type pneumococci carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved protective antigens is urgently needed. Here, we performed intranasal immunization mice membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP gave excellent serotype-independent protection against IPD that was antibody dependent but...

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal associated with increased risk long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during meningitis, damaged a neuroinflammatory response deleterious action toxins in brain. However, little known about invasion pattern pneumococcus into Using bacteremia-derived mouse model, we combined 3D whole...

Pneumococci are the major cause of bacterial meningitis globally. To pneumococci interact with 2 endothelial receptors, polymeric immunoglobulin receptor (pIgR) and platelet cell adhesion molecule (PECAM-1), to penetrate blood-brain barrier (BBB) invade brain.C57BL/6 mice were infected intravenously bioluminescent pneumococci, treated ceftriaxone (1 hour postinfection) anti-pIgR PECAM-1 antibodies or 5 hours postinfection), then monitored for 10 days. Bacterial brain invasion was analyzed...

ABSTRACT Streptococcus pneumoniae (pneumococcus) is a Gram-positive bacterium that causes serious invasive diseases, such as pneumonia, bacteremia, and meningitis, with high morbidity mortality throughout the world. Before causing disease, S. encounters cellular barriers, which are often composed of endothelial cells, like alveolar-capillary barrier blood-brain barrier. adheres to cells may invade them, requires an efficient host response intracellular bacteria. The precise fate during...

Importance A diagnosis of bacterial meningitis in childhood can lead to permanent neurological disabilities. Few studies have examined long-term consequences for work ability adulthood. Objective To compare earnings, loss, and educational attainment between adults diagnosed with population comparators. Design, Setting, Participants This nationwide registry-based matched cohort study included individuals Sweden (aged <18 years) from January 1, 1987, December 31, 2019, general...