E-BUGS-133 - Transcription profiling by array of Streptococcus pneumoniae to identify genes upregulated in distinct niches during pathogenesis after intranasal infection of mice with serotype 4 or 6A pneumococci
Released on 20 July 2012, last updated on 1 May 2014
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 (delta malX) was significantly attenuated for virulence in the lungs, two (delta aliA and delta ilvH) were significantly attenuated for virulence in the blood relative to the wild type, and two others (delta cbiO and delta 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. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-133]
transcription profiling by array
Identification of genes that contribute to the pathogenesis of invasive pneumococcal disease by in vivo transcriptomic analysis. Ogunniyi AD, Mahdi LK, Trappetti C, Verhoeven N, Mermans D, Van der Hoek MB, Plumptre CD, Paton JC. :3268-3278 (2012), PMID:22778095
A functional genomics catalogue of activated transcription factors during pathogenesis of pneumococcal disease. Mahdi LK, Deihimi T, Zamansani F, Fruzangohar M, Adelson DL, Paton JC, Ogunniyi AD, Ebrahimie E. :769 (2014), PMID:25196724
Identification of Genes That Contribute to the Pathogenesis of Invasive Pneumococcal Disease by In Vivo Transcriptomic Analysis. Abiodun D. Ogunniyia, Layla K. Mahdia,Claudia Trappettia,Nadine Verhoevena,Daphne Mermansa,Mark B. Van der Hoekb,Charles D. Plumptrea and James C. Patona.
A transcription factor contributes to pathogenesis and virulence in Streptococcus pneumoniae. Mahdi LK, Ebrahimie E, Adelson DL, Paton JC, Ogunniyi AD. :e70862 (2013), PMID:23967124