A5025747298- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Bacterial Infections and Vaccines
- Streptococcal Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Otolaryngology and Infectious Diseases
- COVID-19 Clinical Research Studies
- Antimicrobial Resistance in Staphylococcus
- Tuberculosis Research and Epidemiology
- Gut microbiota and health
- Brucella: diagnosis, epidemiology, treatment
- Antibiotic Resistance in Bacteria
- Tracheal and airway disorders
- Influenza Virus Research Studies
- Clostridium difficile and Clostridium perfringens research
- Platelet Disorders and Treatments
- SARS-CoV-2 detection and testing
- COVID-19 epidemiological studies
- Bacteriophages and microbial interactions
- Infective Endocarditis Diagnosis and Management
- Antibiotics Pharmacokinetics and Efficacy
- Lung Cancer Research Studies
- Neonatal and Maternal Infections
- Biochemical and Structural Characterization
Radboud University Nijmegen
2014-2025
Radboud University Medical Center
2014-2025
Radboud Institute for Molecular Life Sciences
2014-2025
University Medical Center
2020-2025
Philips (Netherlands)
2021
Boston Children's Hospital
2011
Erasmus MC - Sophia Children’s Hospital
2007
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
1985
University of Maryland, Baltimore
1985
Advanced age is associated with chronic low-grade inflammation, which usually referred to as inflammaging. Elderly are also known have an altered gut microbiota composition. However, whether inflammaging a cause or consequence of composition not clear. In this study, from young old conventional mice was transferred germ-free (GF) mice. Four weeks after transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes conventionalized GF were analyzed by flow cytometry....
Males and females are known to have gender-specific differences in their immune system gut microbiota composition. Whether these composition a cause or consequence of the is not known. To investigate this issue, from conventional males was transferred germ-free animals same opposing gender. We demonstrate that microbiota-independent gender immunity already present mice. In particular type I interferon signaling enhanced intestine females. Presumably, due bacterial groups such as Alistipes,...
Abstract Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection (re)infection, the dynamics of mucosal during primary infection and their potential impact on viral load resolution disease symptoms remain unclear. During first pandemic wave, we assessed longitudinal nasal antibody response index cases with mild COVID-19 household contacts. Nasal serum responses were analysed for up to nine months. Higher receptor binding domain spike...
Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and quadrivalent vaccine, determined if concurrent administration would effects on safety or immunogenicity.TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at Radboud University Medical Centre,...
Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms selected response tissue repair genes contribute susceptibility severity RA. Polymorphisms TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 TLR4 were genotyped 376 Caucasian RA patients 463 healthy controls using single base extension. Genotype distributions compared with those controls. In addition, association need for...
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- long-chain β2→1-fructan for 5 days. Immune cell populations the spleen, mesenteric lymph nodes (MLNs), Peyer's patches (PPs) were analyzed with flow cytometry,...
Meningitis is the most serious of invasive infections caused by Gram-positive bacterium Streptococcus pneumoniae. Vaccines protect only against a limited number serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into molecular pathogenesis pneumococcal disease required in order enable development new or adjunctive treatments and/or vaccines that are efficient across serotypes. We applied genomic array footprinting (GAF) search for S. pneumoniae...
Bacterial respiratory tract infections, mainly caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are among the leading causes of global mortality morbidity. Increased resistance these pathogens to existing antibiotics necessitates search for novel targets develop potent antimicrobials. Here, we report a proof concept study reliable identification potential drug in human combining high-density transposon mutagenesis, high-throughput sequencing, integrative...
Pneumococcal conjugate vaccines (PCVs) have been highly effective in preventing invasive pneumococcal disease. However, increasing serotype coverage of PCVs led to decreasing antibody responses against individual serotypes, possibly leading vaccine failure. It is therefore important improve the immunogenicity PCVs. A novel, synthetic carbohydrate fatty acid monosulphate-based adjuvant squalane-based oil-in-water (CMS:O/W), has proven be safe and potent for protein-based vaccines. Here, we...
In the Netherlands, 7-valent pneumococcal conjugate vaccine (PCV) was introduced to childhood immunization programme in 2006 and replaced by 10-valent PCV (PCV10, GSK) 2011. To describe invasive disease era of vaccination on bacteraemia across all ages, we collected sequenced 979 blood isolates from consecutive patients with Gelderland area, between 2000 2020. total, 58% cases ( n =563/979) occurred elderly population. Compared pre-PCV period (2000–2005), odds ratio for non-PCV10 17.5 (CI...
We applied a novel negative selection strategy called genomic array footprinting (GAF) to identify genes required for genetic transformation of the gram-positive bacterium Streptococcus pneumoniae. Genome-wide mariner transposon mutant libraries in S. pneumoniae strain R6 were challenged by with an antibiotic resistance cassette and growth presence corresponding antibiotic. The GAF screen identified enrichment mutants two genes, i.e., hexA hexB, counterselection 21 different during...
Streptococcus pneumoniae and Staphylococcus aureus cause significant morbidity mortality worldwide. We investigated both the colonization co-colonization characteristics for these pathogens among 250 healthy children from 2 to 5 years of age in Merida, Venezuela, 2007. The prevalence S. colonization, pneumoniae–S. was 28%, 56%, 16%, respectively. Pneumococcal serotypes 6B (14%), 19F (12%), 23F 15 (9%), 6A (8%), 11 23A (6%), 34 (6%) were most prevalent. Non-respiratory atopy a risk factor (p...
Since Streptococcus pneumoniae transmits through droplet spread, this respiratory tract pathogen may be able to survive in saliva. Here, we show that saliva supports survival of clinically relevant S. strains for more than 24 h a capsule-independent manner. Moreover, induced growth growth-permissive conditions, suggesting is well adapted uptake nutrients from bodily fluid. By using Tn-seq, method genome-wide negative selection screening, identified 147 genes potentially required and saliva,...
Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit emergence new variants, it essential to induce broad restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying variable N terminus...
Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with wide spectrum disease severity. Besides environmental and genetic factors, it thought that the innate immune system plays pivotal role. The aim this study was to investigate expression receptors on monocytes vitro responsiveness from severe RSV infections.Peripheral blood mononuclear cells (PBMCs) infections were isolated. Classical, intermediate nonclassical immunophenotyped for CD14, CD16, human leukocyte...
Platelets are increasingly recognized to play a role in the complications of Streptococcus pneumoniae infections. S. expresses neuraminidases, which may alter glycans on platelet surface.
Abstract Background Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution genetic variation to IPD phenotype. Methods The index cohort consisted 349 patients admitted 2 Dutch hospitals between 2000–2011 with bacteremia. We performed genome-wide association studies identify lineages, genes, and allelic variants associated 23 phenotypes. identified associations were validated in...
Although carbon dioxide (CO2) is known to be essential for Streptococcus pneumoniae growth, it poorly understood how this respiratory tract pathogen adapts the large changes in environmental CO2 levels encounters during transmission, host colonization, and disease. To identify molecular mechanisms that facilitate pneumococcal growth under CO2-poor conditions, we generated a random S. R6 mariner transposon mutant library representing mutations 1,538 different genes exposed ambient air. With...
To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated association between genotype Streptococcus pneumoniae and outcomes for 349 bacteremic patients. A genome-wide study (GWAS) demonstrated a strong correlation 30-day mortality presence phage-derived gene pblB, encoding platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players innate immune system, in sepsis,...
The respiratory pathogen Streptococcus pneumoniae is a major cause of diseases such as otitis media, pneumonia, sepsis and meningitis. first step towards infection colonization the nasopharynx. Recently, it was shown that agglutinating antibodies play an important role in prevention mucosal with S. pneumoniae. Here, we present novel method to quantify antibody-dependent pneumococcal agglutination high-throughput manner using flow cytometry. We found concentration against capsule are directly...
Although the Streptococcus pneumoniae polysaccharide capsule is an important virulence factor, ~ 15% of carriage isolates are nonencapsulated. Nonencapsulated S. a cause mucosal infections. Recent studies have shown that neutrophils kill predominately through neutrophil proteases, such as elastase and cathepsin G. Another recent finding nonencapsulated pneumococci greater resistance to resist cationic antimicrobial peptides in immunity. We here show extracellular human elastase- G-mediated...
Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infections in infants. A small percentage the infected infants develops a severe infection, while most these severely ill patients were previously healthy. It remains unclear why children develop RSV infections. In this study, we investigate whether pneumococcal nasopharyngeal carriage patterns correlate with mucosal inflammation and severity disease. total, 105 hospitalized infection included recovery samples...
To examine the association between bacterial-viral co-occurrence in nasopharynx and risk of community acquired pneumonia (CAP) young children living resource-limited settings.A case-control study was conducted January December 2017 Moshi, Tanzania. Children 2-59 months with CAP healthy controls were enrolled. RSV Influenza A/B detected a standardized polymerase chain reaction (PCR) method, simplified real-time quantitative PCR without sample pre-processing, developed to detect bacterial...