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Title: The role of the blood-brain barrier during pneumococcal meningitis
Author: Panagiotou, S.
ISNI:       0000 0004 6058 7253
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Background: Pneumococcal meningitis remains the main cause of severe bacterial meningitis in children and adults (1); in February, 2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) was approved by the FDA, which was presented as a successor to the 7-valent conjugate vaccine (PCV7) (2). Nonetheless, no vaccine provides protection against more than 90 serotypes of Streptococcus pneumoniae. In 2013, 2.8 million children died before completing one month of being born because of the pneumococcus. Methods: Pneumococcal survival, adherence and invasion were assessed using human brain cells and an entirely human Blood-Brain Barrier model. Additionally, the role of pneumolysin during infection was investigated. Having access to a broad library of genes, host responses against pneumococcal infection were investigated. Results: Pneumolysin enhances pneumococcal survival, and increases adherence and invasiveness. Toxin pore formation leads to tight junctions disruption and impaired cytoskeletal functions. Pneumolysin concentration was in accordance to serotype virulence. Serotype 6B exhibited high CFUs during infection in the Blood-brain barrier. Its pneumolysin concentrations suggest that Streptococcus pneumoniae uses multiple pathways to traverse to the abluminal side. Host immune responses contributed further to tight junction dissociation, revealing synergism between the host and the pathogen during pathogenesis progression.
Supervisor: Kadioglu, A. K. ; Patabendige, A. P. ; Solomon, T. S. ; Griffiths, M. J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral