Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/73697
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Identification of genes that contribute to the pathogenesis of invasive Pneumococcal Disease by in vivo transcriptomic analysis
Author: Ogunniyi, A.
Mahdi, L.
Trappetti, C.
Verhoeven, N.
Mermans, D.
Van der Hoek, M.
Plumptre, C.
Paton, J.
Citation: Infection and Immunity, 2012; 80(9):3268-3278
Publisher: Amer Soc Microbiology
Issue Date: 2012
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Abiodun D. Ogunniyi, Layla K. Mahdi, Claudia Trappetti, Nadine Verhoeven, Daphne Mermans, Mark B. Van der Hoek, Charles D. Plumptre and James C. Paton
Abstract: Streptococcus pneumoniae (the pneumococcus) continues to be responsible for a high level of global morbidity and mortality resulting from pneumonia, bacteremia, meningitis, and otitis media. Here we have used a novel technique involving niche-specific, genome-wide in vivo transcriptomic analyses to identify genes upregulated in distinct niches during pathogenesis after intranasal infection of mice with serotype 4 or 6A pneumococci. The analyses yielded 28 common, significantly upregulated genes in the lungs relative to those in the nasopharynx and 25 significantly upregulated genes in the blood relative to those in the lungs in both strains, some of which were previously unrecognized. The role of five upregulated genes from either the lungs or the blood in pneumococcal pathogenesis and virulence was then evaluated by targeted mutagenesis. One of the mutants (∆malX) was significantly attenuated for virulence in the lungs, two (∆aliA and ∆ilvH) were significantly attenuated for virulence in the blood relative to the wild type, and two others (∆cbiO and ∆piuA) were completely avirulent in a mouse intranasal challenge model. We also show that the products of aliA, malX, and piuA are promising candidates for incorporation into multicomponent protein-based pneumococcal vaccines currently under development. Importantly, we suggest that this new approach is a viable complement to existing strategies for the discovery of genes critical to the distinct stages of invasive pneumococcal disease and potentially has broad application for novel protein antigen discovery in other pathogens such as S. pyogenes, Haemophilus influenzae type b, and Neisseria meningitidis.
Keywords: Nasopharynx; Animals; Mice; Streptococcus pneumoniae; Bacteremia; Pneumococcal Infections; Pneumonia, Bacterial; Virulence Factors; Gene Expression Profiling
Rights: Copyright © 2012 by the American Society for Microbiology.
RMID: 0020121951
DOI: 10.1128/IAI.00295-12
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.