Streptococcus pneumoniae serotype 1 displays some unusual epidemiological, clinical and microbiological characteristics. In Africa, serotype 1 is the leading serotype causing invasive pneumococcal diseases, including, pneumonia, meningitis and sepsis. Unusually, serotype 1 is rarely detected during routine nasopharyngeal swabbing, even in areas of high disease burden. S. pneumoniae are natural commensals of the nasopharynx and colonisation of this area has been described as a pre-requisite for invasive disease, hence little is understood about why serotype 1 carriage rates are so low, whilst burden of disease is so high. This body of work sought to identify key virulence factors associated with serotype 1 disease pathogenesis and the effect these have on nasopharyngeal colonisation and progression from carriage to invasive disease. Murine models of nasopharyngeal carriage, pneumonia and sepsis were used to study serotype 1 pathogenesis and identified the bacterial toxin pneumolysin, and autolysin as key virulence factors associated with disease pathogenesis. In addition, the influence of serotype 1 infection on the host immune responses in murine models of pneumococcal infection was also addressed. Current pneumococcal vaccines (PCV13) include serotype 1 however, the impact of this vaccination in reducing serotype 1 disease burden is still unknown. Findings here suggest that pneumolysin, not bacterial capsule should be a target for strong consideration in future vaccine design. New therapeutics should also be designed to target pneumolysin as it is in the main driver of pathogenesis in the context of pneumococcal disease, particularly in serotype 1 infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:733910 |
| Date | January 2017 |
| Creators | Jacques, L. C. |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/3011232/ |
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