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

Mahdi, Layla K. and Wang, Hui and Van der Hoek, Mark B. and 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. ISSN 0021-9738

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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.


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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 3.0.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Nursing
Date Deposited: 03 Aug 2016 23:56
Last Modified: 20 Mar 2017 23:19
Fields of Research : 06 Biological Sciences > 0605 Microbiology > 060501 Bacteriology
11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
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
Funding Details:
Identification Number or DOI: 10.1172/JCI45850
URI: http://eprints.usq.edu.au/id/eprint/28819

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