Search

Your search keyword '"Weiser, J.N."' showing total 14 results
Start Over Author "Weiser, J.N."
14 results on '"Weiser, J.N."'

1. E-cigarette Whole Body Aerosol Exposure: Acute Cardiovascular Changes and Effects on Subsequent Pneumococcus Infection

Author

Grunig, G., primary, Ye, C., additional, Voynov, D., additional, Raja, A., additional, Durmus, N., additional, Goriainova, V., additional, Joung, H., additional, Pehlivan, A., additional, Abruzzo, A., additional, Chalupa, D., additional, Kwon, S., additional, Nolan, A., additional, Weiser, J.N., additional, Elder, A.C.P., additional, and Zelikoff, J.T., additional

Published
2023
Full Text
View/download PDF

2. Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system

Author

Sebert, M.E., Patel, K.P., Plotnick, M., and Weiser, J.N.

Subjects
Genetic transformation -- Research, Streptococcus pneumoniae -- Genetic aspects, Genetic research, Biological sciences
Abstract

Activation of the CiaRH two-component signaling system prevents the development of competence for genetic transformation in Streptococcus pneumoniae through a previously unknown mechanism. Earlier studies have shown that CiaRH controls the expression of htrA, which we show encodes a surface-expressed serine protease. We found that mutagenesis of the putative catalytic serine of HtrA, while not impacting the competence of a [ciaRH.sup.+] strain, restored a normal competence profile to a strain having a mutation that constitutively activates the CiaH histidine kinase. This result implies that activity of HtrA is necessary for the CiaRH system to inhibit competence. Consistent with this finding, recombinant HtrA (rHtrA) decreased the competence of pneumococcal cultures. The rHtrA-mediated decline in transformation efficiency could not he corrected with excess competence-stimulating peptide (CSP), suggesting that HtrA does not act through degradation of this signaling molecule. The inhibitory effects of rHtrA and activated CiaH, however, were largely overcome in a strain having constitutive activation of the competence pathway through a mutation in the cytoplasmic domain of the CoreD histidine kinase. Although these results suggested that HtrA might act through degradation of the extracellular portion of the Cored receptor, Western immunoblots for Cored did not reveal changes in protein levels attributable to HtrA. We therefore postulate that HtrA may act on an unknown protein target that potentiates the activation of the ComDE system by CSP. These findings suggest a novel regulatory role for pneumococcal HtrA in modulating the activity of a two-component signaling system that controls the development of genetic competence.

Published
2005

3. Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage

Author

Mitsi, E., Roche, A.M., Reine, J., Zangari, T., Owugha, J.T., Pennington, S.H., Gritzfeld, J.F., Wright, A.D., Collins, A.M., Selm, S. van, Jonge, M.I. de, Gordon, S.B., Weiser, J.N., and Ferreira, D.M.

Subjects
qw_640, qw_4, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], wc_217
Abstract

Contains fulltext : 170601.pdf (Publisher’s version ) (Open Access) The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.

Published
2017

4. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Author

Lees, J.A., Ferwerda, B., Kremer, P.H.C., Wheeler, N.E., Seron, M.V., Croucher, N.J., Gladstone, R.A., Bootsma, H.J., Rots, N.Y., Wijmega-Monsuur, A.J., Sanders, E.A. (Elisabeth), Trzcinski, K., Wyllie, AL, Zwinderman, A.H. (Ailko), Berg, L.H. (Leonard) van den, Rheenen, W. (Wouter) van, Veldink, J.H. (Jan), Harboe, Z.B., Lundbo, L.F., Groot, L., Schoor, N.M., van der Velde, N., Angquist, LH, Sorensen, H.G., Nohr, C. (Christian), Mentzer, A.J., Mills, T.C., Knight, J.C. (Julian), Plessis, M. (Michelle) du, Nzenze, S., Weiser, J.N., Parkhill, J. (Julian), Madhi, S., Benfield, T., von Gottberg, A., Ende, A. (A.) van der, Brouwer, MC, Barrett, JC, Bentley, S.D., van de Beek, D.., Lees, J.A., Ferwerda, B., Kremer, P.H.C., Wheeler, N.E., Seron, M.V., Croucher, N.J., Gladstone, R.A., Bootsma, H.J., Rots, N.Y., Wijmega-Monsuur, A.J., Sanders, E.A. (Elisabeth), Trzcinski, K., Wyllie, AL, Zwinderman, A.H. (Ailko), Berg, L.H. (Leonard) van den, Rheenen, W. (Wouter) van, Veldink, J.H. (Jan), Harboe, Z.B., Lundbo, L.F., Groot, L., Schoor, N.M., van der Velde, N., Angquist, LH, Sorensen, H.G., Nohr, C. (Christian), Mentzer, A.J., Mills, T.C., Knight, J.C. (Julian), Plessis, M. (Michelle) du, Nzenze, S., Weiser, J.N., Parkhill, J. (Julian), Madhi, S., Benfield, T., von Gottberg, A., Ende, A. (A.) van der, Brouwer, MC, Barrett, JC, Bentley, S.D., and van de Beek, D..

Abstract

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause lifethreatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved i

Published
2019
Full Text
View/download PDF

11. Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniaelung infection

Author

Wang, Y., Jiang, B., Guo, Y., Li, W., Tian, Y., Sonnenberg, G.F., Weiser, J.N., Ni, X., and Shen, H.

Abstract

Pneumonia caused by Streptococcus pneumoniae(Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced, and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Spstrains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology, and apoptosis of lung epithelial cells. Spinfection in the lung induced strong T-helper type 17 (Th17) responses at the lung mucosal site. Transfer of CD4+T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by interleukin-17A (IL-17A) blockade. Transfer of memory CD4+T cells from IL-17A-knockout mice failed to provide protection. These results indicate that memory Th17 cells had a key role in providing protection against pneumonia in a serotype-independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells.

Published
2017
Full Text
View/download PDF

13. Differential protein expression in phenotypic variants of Streptococcus pneumoniae

Author

Overweg, K. (Karin), Pericone, C.D., Verhoef, G.G., Weiser, J.N., Meiring, H.D., Jong, A.P. de, Groot, R. (Ronald) de, Hermans, P.W.M. (Peter), Overweg, K. (Karin), Pericone, C.D., Verhoef, G.G., Weiser, J.N., Meiring, H.D., Jong, A.P. de, Groot, R. (Ronald) de, and Hermans, P.W.M. (Peter)

Abstract

Streptococcus pneumoniae undergoes spontaneous phase variation resulting in opaque and transparent colony forms. Differences in colony opacity correlate with differences in virulence: the transparent variants are more capable of colonizing the nasopharynx, whereas the opaque variants show increased virulence during systemic infections. To gain insight into the pathogenesis of pneumococcal disease at the molecular level, protein expression patterns of the phenotypic variants of two pneumococcal strains were compared by high-resolution two-dimensional protein electrophoresis. In comparison with transparent variants, the opaque variants reduced the expression of two proteins and overexpressed one protein. The proteins were identified by mass spectrometric analysis. The protein overexpressed in the opaque phenotype revealed significant homology to elongation factor Ts of Helicobacter pylori. One of the two proteins that were underexpressed in the opaque variants revealed significant homology to the proteinase maturation protein PrtM of Lactocobacillus paracasei, a member of the family of peptidyl-prolyl cis/trans isomerases. A consensus lipoprotein signal sequence suggests that the putative proteinase maturation protein A, designated PpmA, is located at the surface of the pneumococcus and may play a role in the maturation of surface or secreted proteins. The second underexpressed protein was identified as pyruvate oxidase, SpxB. The lower SpxB expression in opaque variants most probably explains the reduced production of hydrogen peroxide, a reaction product of SpxB, in this variant. Since a spxB-defective pneumococcal mutant has decreased ability to colonize the nasopharynx (B. Spellerberg, D. R. Cundell, J. Sandros, B. J. Pearce, I. Idanpaan-Heikkila, C. Rosenow, and H. R. Masure, 1996. Mol. Microbiol. 19:803-813, 1996), our data suggest that SpxB plays an important role in enhancing the ability of transparent variants to efficiently colonize the nasopharynx.

Published
2000

14. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract

Author

Jesper Reinholdt, Mogens Kilian, Nataro, J.P., Cohen, P.S., Mobley, H.L.T., and Weiser, J.N.

Subjects
Proteases, biology, Neisseria meningitidis, biology.organism_classification, medicine.disease_cause, Capnocytophaga, Moraxella nonliquefaciens, Virology, Haemophilus influenzae, Microbiology, fluids and secretions, stomatognathic system, Streptococcus pneumoniae, medicine, Pathogen, Bacteria
Abstract

The three principal causes of bacterial meningitis, Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, produce an IgA1 protease. In addition, IgA1 proteases are produced by two urogenital pathogens, five species of commensal gram-positive cocci found in the pharynx and oral cavity, H. parahaemolyticus, and all human-associated species of the genera Capnocytophaga and Prevotella. In accordance with the substrate specificity of IgA1 proteases, humans and hominoid primates are the exclusive hosts of the bacteria that produce these enzymes. This chapter presents the hypothesis that invasive infection in occasional individuals is a result of nonsynchronized induction of the two types of antibodies by successive encounters with two different microorganisms: (i) colonization in the gut or upper respiratory tract with bacteria expressing surface epitopes similar or identical to those of the respective pathogen (e.g., E. coli K100 in the case of H. influenzae type b, and E. coli K1 or Moraxella nonliquefaciens in the case of N. meningitidis group B), and (ii) subsequent colonization with the actual pathogen. As a result of the prior colonization with a cross-reactive microorganism, the pathogen encounters preexisting IgA1 antibodies to its surface epitopes but no antibodies that will neutralize its IgA1 protease. IgA1s of humans and hominoid primates were the only known substrates of IgA1 proteases until recently. Now other permissive substrates have been revealed. Most of these are proteins of immunological relevance, but for some of the substrates, their accessibility to IgA1 protease in vivo is a matter of speculation.

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results