Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

Article


Mahdi, Layla K., Wang, Hui, Van der Hoek, Mark B., Paton, James C. and Ogunniyi, Abiodun D.. 2012. "Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice." Journal of Clinical Investigation. 122 (6), pp. 2208-2220. https://doi.org/10.1172/JCI45850
Article Title

Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

ERA Journal ID16336
Article CategoryArticle
AuthorsMahdi, Layla K. (Author), Wang, Hui (Author), Van der Hoek, Mark B. (Author), Paton, James C. (Author) and Ogunniyi, Abiodun D. (Author)
Journal TitleJournal of Clinical Investigation
Journal Citation122 (6), pp. 2208-2220
Number of Pages13
Year2012
Place of PublicationUnited States
ISSN0021-9738
1558-8238
Digital Object Identifier (DOI)https://doi.org/10.1172/JCI45850
Web Address (URL)https://www.jci.org/articles/view/45850
Abstract

Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H2O2. A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens.

ANZSRC Field of Research 2020310701. Bacteriology
320701. Medical bacteriology
Byline AffiliationsUniversity of Adelaide
Institution of OriginUniversity of Southern Queensland
Funding source
NHMRC
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