Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota.

Background: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.

Airway macrophages display decreased expression of receptors mediating and regulating scavenging in early cystic fibrosis lung disease.

Background: Cystic fibrosis (CF) airway disease is characterized by chronic inflammation, featuring neutrophil influx to the lumen. Airway macrophages (AMs) can promote both inflammation and resolution, and are thus critical to maintaining and restoring homeostasis. CF AM functions, specifically scavenging activity and resolution of inflammation, have been shown to be impaired, yet underlying processes remain unknown.

Mycoplasma pneumoniae Compared to Streptococcus pneumoniae Avoids Induction of Proinflammatory Epithelial Cell Responses despite Robustly Inducing TLR2 Signaling.

Mycoplasma pneumoniae and Streptococcus pneumoniae are the most common bacterial causes of pneumonia in children. The clinical characteristics of pneumonia differ significantly between the two bacteria. We aimed to elucidate the differences in pathogenesis between M.

carriage evades induction of protective mucosal antibodies.

Background: is the most common bacterial cause of pneumonia in children hospitalised for community-acquired pneumonia (CAP). Prevention of infection by vaccines may be an important strategy in the presence of emerging macrolide-resistant However, knowledge of immune responses to is limited, complicating vaccine design.

Methods: We studied the antibody response during respiratory tract infection and asymptomatic carriage in two different cohorts.

Real-Time Monitoring of Beer Parameters Using Infrared Spectroscopy-A Process Analytical Technology Approach.

Background: Quality assessment of a finished beer product is usually performed by determining whether a sample from the batch conforms to the specifications and industry standards. However, if one or more quality parameters do not meet specifications, the batch must be reprocessed or even disposed of entirely.

Objective: The aim of this work was to propose real-time monitoring of beer parameters using infrared spectroscopy, according to the process analytical technology (PAT) approach.

Antibodies to Protein but Not Glycolipid Structures Are Important for Host Defense against Mycoplasma pneumoniae.

Antibody responses to correlate with pulmonary clearance. However, -specific IgG antibodies can cross-react with the myelin glycolipid galactocerebroside (GalC) and cause neurological disorders. We assessed whether antiglycolipid antibody formation is part of the physiological immune response to We show that antibodies against proteins and glycolipids arise in serum of -infected children and mice.

The impact of parallel regulatory-health technology assessment scientific advice on clinical development. Assessing the uptake of regulatory and health technology assessment recommendations.

Aims: The parallel regulatory-health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought.

Methods: Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed.

The Role of B Cells in Carriage and Clearance of Mycoplasma pneumoniae From the Respiratory Tract of Mice.

Background: Carriage of Mycoplasma pneumoniae (Mp) in the nasopharynx is considered a prerequisite for pulmonary infection. It is interesting to note that Mp carriage is also detected after infection. Although B cells are known to be involved in pulmonary Mp clearance, their role in Mp carriage is unknown.

Uncoupling of the apyrimidinic/apurinic endonucleolytic and 3'→5' exonucleolytic activities of the Nfo protein of Mycoplasma pneumoniae through mutation of specific amino acid residues.

The DNA recombination and repair machineries of Mycoplasma pneumoniae and Mycoplasma genitalium were predicted to consist of a set of ~11 proteins. The function of one of these proteins was inferred from its homology with proteins belonging to the Endo IV enzyme family. The members of this family function in the repair of apyrimidinic/apurinic (AP) sites in DNA.

Functional analysis of the superfamily 1 DNA helicases encoded by Mycoplasma pneumoniae and Mycoplasma genitalium.

The DNA recombination and repair machinery of Mycoplasma pneumoniae is composed of a limited set of approximately 11 proteins. Two of these proteins were predicted to be encoded by neighboring open reading frames (ORFs) MPN340 and MPN341. Both ORFs were found to have sequence similarity with genes that encode proteins belonging to the DNA helicase superfamily 1 (SF1).

Increased CD4(+) T cell co-inhibitory immune receptor CEACAM1 in neonatal sepsis and soluble-CEACAM1 in meningococcal sepsis: a role in sepsis-associated immune suppression?

The co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an increased percentage CEACAM1 positive CD4(+) T-cells.

The RuvA homologues from Mycoplasma genitalium and Mycoplasma pneumoniae exhibit unique functional characteristics.

The DNA recombination and repair machineries of Mycoplasma genitalium and Mycoplasma pneumoniae differ considerably from those of gram-positive and gram-negative bacteria. Most notably, M. pneumoniae is unable to express a functional RecU Holliday junction (HJ) resolvase.

Functional characterization of the RuvB homologs from Mycoplasma pneumoniae and Mycoplasma genitalium.

Homologous recombination between repeated DNA elements in the genomes of Mycoplasma species has been hypothesized to be a crucial causal factor in sequence variation of antigenic proteins at the bacterial surface. To investigate this notion, studies were initiated to identify and characterize the proteins that form part of the homologous DNA recombination machinery in Mycoplasma pneumoniae as well as Mycoplasma genitalium. Among the most likely participants of this machinery are homologs of the Holliday junction migration motor protein RuvB.

Variation in a surface-exposed region of the Mycoplasma pneumoniae P40 protein as a consequence of homologous DNA recombination between RepMP5 elements.

Mycoplasma pneumoniae is a human pathogen that causes a range of respiratory tract infections. The first step in infection is adherence of the bacteria to the respiratory epithelium. This step is mediated by a specialized organelle, which contains several proteins (cytadhesins) that have an important function in adherence.

Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.

T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions.

Strain-specific impact of PsaR of Streptococcus pneumoniae on global gene expression and virulence.

Previous studies have indicated that PsaR of Streptococcus pneumoniae is a manganese-dependent regulator, negatively affecting the expression of at least seven genes. Here, we extended these observations by transcriptome and proteome analysis of psaR mutants in strains D39 and TIGR4. The microarray analysis identified three shared PsaR targets: the psa operon, pcpA and prtA.

Site-specific contributions of glutamine-dependent regulator GlnR and GlnR-regulated genes to virulence of Streptococcus pneumoniae.

The transcriptional regulator GlnR of Streptococcus pneumoniae is involved in the regulation of glutamine and glutamate metabolism, controlling the expression of the glnRA and glnPQ-zwf operons, as well as the gdhA gene. To assess the contribution of the GlnR regulon to virulence, D39 wild-type and mutant strains lacking genes of this regulon were tested in an in vitro adherence assay and murine infection models. All of the mutants, except the DeltaglnR mutant, were attenuated in adherence to human pharyngeal epithelial Detroit 562 cells, suggesting a contribution of these genes to adherence during the colonization of humans.

CodY of Streptococcus pneumoniae: link between nutritional gene regulation and colonization.

CodY is a nutritional regulator mainly involved in amino acid metabolism. It has been extensively studied in Bacillus subtilis and Lactococcus lactis. We investigated the role of CodY in gene regulation and virulence of the human pathogen Streptococcus pneumoniae.

Clinical and molecular epidemiologic characteristics of coagulase-negative staphylococcal bloodstream infections in intensive care neonates.

Objectives: This study aimed to determine clinical characteristics of coagulase-negative staphylococcal (CoNS) sepsis in neonates, to assess the molecular epidemiology and biofilm forming properties of isolated strains, and to assess antibiotic susceptibility of clonal compared with incidentally occurring strains.

Methods: We performed a retrospective study on late-onset CoNS sepsis in infants in the neonatal intensive care unit of a Dutch university hospital in 2003. CoNS isolates were genotyped by restriction fragment end labeling and pulsed-field gel electrophoresis.

Development of lactococcal GEM-based pneumococcal vaccines.

We report the development of a novel protein-based nasal vaccine against Streptococcus pneumoniae, in which three pneumococcal proteins were displayed on the surface of a non-recombinant, killed Lactococcus lactis-derived delivery system, called Gram-positive Enhancer Matrix (GEM). The GEM particles induced the production of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) by macrophages as well as the maturation of dendritic cells. The pneumococcal proteins IgA1 protease (IgA1p), putative proteinase maturation protein A (PpmA) and streptococcal lipoprotein A (SlrA) were anchored in trans to the surface of the GEM particles after recombinant production of the antigens in L.

Identification and characterization of a novel outer membrane protein (OMP J) of Moraxella catarrhalis that exists in two major forms.

Moraxella catarrhalis is a common commensal of the human respiratory tract that has been associated with a number of disease states, including acute otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. During studies to investigate the outer membrane proteins of this bacterium, two novel major proteins, of approximately 19 kDa and 16 kDa (named OMP J1 and OMP J2, respectively), were identified. Further analysis indicated that these two proteins possessed almost identical gene sequences, apart from two insertion/deletion events in predicted external loops present within the putative barrel-like structure of the proteins.

The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization.

Streptococcus pneumoniae expresses two surface-exposed lipoproteins, PpmA and SlrA, which share homology with distinct families of peptidyl-prolyl isomerases (PPIases). In this study, we demonstrated for the first time that the lipoprotein cyclophilin, SlrA, can catalyze the cis-trans isomerization of proline containing tetrapeptides and that SlrA contributes to pneumococcal colonization. The substrate specificity of SlrA is typical for prokaryotic and eukaryotic cyclophilins, with Suc-Ala-Ala-Pro-Phe-p-nitroanilide (pNA) being the most rapidly catalyzed substrate.

The Ami-AliA/AliB permease of Streptococcus pneumoniae is involved in nasopharyngeal colonization but not in invasive disease.

The Ami-AliA/AliB oligopeptide permease is an ATP-binding cassette transporter which is found in Streptococcus pneumoniae and which is involved in nutrient uptake. We investigated the role of the three paralogous oligopeptide-binding lipoproteins AmiA, AliA, and AliB by using murine models of pneumococcal colonization and invasive disease. A series of mutants lacking aliA, aliB, and amiA either alone or in combination as double or triple mutations were used.