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Role of the secretome of Neisseria meningitidis in infection and protection

Projectomschrijving

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Titel: A novel phase-variable autotransporter, AusI, of Neisseria meningitidis.
Auteur: P. van Ulsen, B. Adler, P. Fassler, M. Gilbert, M. van Schilfgaarde, P. van der Ley, L. van Alphen, J. Tommassen.
Magazine: Microbes and Infection
Titel: Polar secretion of a family of large bacterial virulence proteins.
Auteur: S. Jain, P. van Ulsen, I. Benz, M. A. Schmidt, R. Fernandez, J. Tommassen, M. B. Goldberg.
Magazine: Journal of Bacteriology
Titel: Protein secretion and secreted proteins in pathogenic Neisseriaceae
Auteur: P. van Ulsen, J. Tommassen
Magazine: FEMS Microbiology Reviews
Titel: Identification of proteins of Neisseria meningitidis induced under iron-limiting conditions using the isobaric tandem mass tag (TMT) labeling approach.
Auteur: P. van Ulsen, K. Kuhn, T. Prinz, H. Legner, P. Schmid, C. Baumann, J. Tommassen
Magazine: Proteomics
Titel: Secreted complement inhibitors by Neisseria meningitidis
Titel: Role of the lipoprotein signal sequence in the secretion and function of the NalP autotransporter of Neisseria meningitidis
Link: http://neisseria.org/ipnc/2008/Abstracts_poster_presentations_IPNC_2008.pdf
Titel: NalP-mediated proteolytic release of the lactoferrin-binding protein B from the meningococcal cell surface
Auteur: V.M.C. Roussel-Jazédé, I. Jongerius, M.P. Bos, J. Tommassen, P. van Ulsen
Magazine: Infection and Immunity
Titel: Processing of the Two-partner secretion A (TpsA) proteins of Neisseria meningitidis by the autotransporter NalP
Link: http://neisseria.org/ipnc/2008/Abstracts_poster_presentations_IPNC_2008.pdf
Titel: A novel IS200/605-like insertion sequence in Neisseria meningitidis associated with clonal complexes cc18 and cc213
Link: http://neisseria.org/ipnc/2008/Abstracts_poster_presentations_IPNC_2008.pdf
Titel: Two-partner secretion systems of Neisseria meningitidis associated with invasive clonal complexes.
Auteur: P. van Ulsen, L. Rutten, M. Feller, J. Tommassen, A. van der Ende.
Magazine: Infection and Immunity
Titel: Coincorporation of LpxL1 and PagL mutant lipopolysaccharides into liposomes with Neisseria meningitidis opacity protein: Influence of endotoxic and adjuvant activity
Auteur: J. Arenas, H. van Dijken, B. Kuipers, H.J. Hamstra, J. Tommassen, P. van der Ley
Magazine: Clinical and Vaccine Immunology
Titel: Channel properties of the translocator domain of the autotransporter Hbp of Escherichia coli
Auteur: Roussel-Jazédé, V., Van Gelder, P., Sijbrandi, R., Rutten, L., Otto, B.R., Luirink, J., Gros, P., Tommassen, J., van Ulsen, P.
Magazine: Molecular Membrane Biology
Titel: Candidate verification of iron-regulated Neisseria meningitidis proteins using isotopic versions of tandem mass tags (TMT) and single reaction monitoring.
Auteur: Byers, H.L., Cambell, J., van Ulsen, P., Tommassen, J., Ward, M.A., Schulz-Knappe, P., Prinz, T., Kuhn, K.
Magazine: Journal of Proteomics
Titel: Structural biology of membrane proteins.
Auteur: P. van Ulsen, P. Gros, J. Tommassen

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Samenvatting van de aanvraag

Pathogenic bacteria secrete proteins into their external milieu. These proteins play a crucial role in establishing disease, for example by enabling host-tissue colonization, damaging host cells or tissues, or by modulating host-cell responses [1]. Neisseria meningitidis is a Gram-negative pathogen that strictly colonizes humans. It inhabits the upper respiratory tract as a commensal, but, occasionally, causes meningitis and/or sepsis, which are severe systemic diseases [2]. Because the human body is its only natural habitat, all proteins that are secreted must have a role in either colonization or infection. Thus, these proteins represent attractive targets for therapeutics and immune intervention, since blocking their function could help in the treatment or prevention of disease. However, the full repertoire of secreted proteins, the secretome, has not been studied to date. The genome sequences of three meningococcal strains are available [3,4,5]. Their analysis suggested the presence of three out of the six protein-secretion pathways that are widely disseminated among Gram-negative bacteria and, depending on the strain, of ~10-15 secreted proteins [6,7]. However, data on the expression and function of these secreted proteins are scarce. Additionally, this analysis revealed the inherent capacity of the bacteria to vary the sequence of some of the secreted proteins through gene conversion [7], as is illustrated in Fig. 1 in Appendix A. This variation may affect the specificity of the secreted protein for its host-cell targets and, thereby, dramatically influence the outcome of colonization or infection. In the proposed project we intend to study the expression and function of the secretome of N. meningitidis in colonization and infection and its vaccine potential. Specifically, we intend to (i) identify and compare the secretome of isolates from carriers and from patients, (ii) establish whether these secreted proteins are expressed in vivo, (iii) elucidate the function of the secreted proteins and identify their host-cell targets, (iv) verify the postulated sequence variation of secreted proteins through gene conversion and study whether such variations affect host-cell target specificity, (v) establish the role of secreted proteins in colonization and infection by exploiting newly established animal models, and (vi) determine their vaccine potential.

Onderwerpen

Kenmerken

Projectnummer:
91206083
Looptijd: 100%
Looptijd: 100 %
2006
2010
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. J.P.M. Tommassen
Verantwoordelijke organisatie:
Universiteit Utrecht