Characterization of pneumococcal genes involved in bloodstream invasion in a mouse model

Mahdi, Layla K. and Van der Hoek, Mark B. and Ebrahimie, Esmaeil and Paton, James C. and Ogunniyi, Abiodun D. (2015) Characterization of pneumococcal genes involved in bloodstream invasion in a mouse model. PLoS One, 10 (11). pp. 1-15.

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Abstract

Streptococcus pneumoniae (the pneumococcus) continues to account for significant morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteremia and meningitis, as well as less serious infections such as sinusitis, conjunctivitis and otitis media. Current polysaccharide vaccines are strictly serotype-specific and also drive the emergence of non-vaccine serotype strains. In this study, we used microarray analysis to compare gene expression patterns of either serotype 4 or serotype 6A pneumococci in the nasopharynx and blood of mice, as a model to identify genes involved in invasion of blood in the context of occult bacteremia in humans. In this manner, we identified 26 genes that were significantly up-regulated in the nasopharynx and 36 genes that were significantly up-regulated in the blood that were common to both strains. Gene Ontology classification revealed that transporter and DNA binding (transcription factor) activities constitute the significantly different molecular functional categories for genes up-regulated in the nasopharynx and blood. Targeted mutagenesis of selected genes from both niches and subsequent virulence and pathogenesis studies identified the manganese-dependent superoxide dismutase (SodA) as most likely to be essential for colonization, and the cell wall-associated serine protease (PrtA) as important for invasion of blood. This work extends our previous analyses and suggests that both PrtA and SodA warrant examination in future studies aimed at prevention and/or control of pneumococcal disease.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Published version made available in accordance with Creative Commons Attribution License 4.0.
Faculty / Department / School: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing
Date Deposited: 14 Jun 2016 05:15
Last Modified: 27 Jan 2017 05:06
Fields of Research : 06 Biological Sciences > 0605 Microbiology > 060501 Bacteriology
06 Biological Sciences > 0605 Microbiology > 060503 Microbial Genetics
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1371/journal.pone.0141816
URI: http://eprints.usq.edu.au/id/eprint/28536

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