Understanding the determinants of pathogenicity in Group A streptococcus



Clarke, J
(2019) Understanding the determinants of pathogenicity in Group A streptococcus. PhD thesis, University of Liverpool.

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Abstract

Background: Streptococcus pyogenes is an important human pathogen responsible for clinical manifestations ranging from mild superficial infections such as pharyngitis to serious invasive infections such as necrotising fasciitis and sepsis. The drivers of these different disease phenotypes are not known. The M surface protein encoded by the emm gene is used to type GAS isolates and is used as an epidemiological marker; over 230 emm types have been described to date. Using in vitro and in vivo models of GAS infection the aim of this thesis was to consider the different pathogenic mechanisms GAS employs to cause serious acute infection, host-immune evasion and chronic infection. Methods: In vitro characteristics such as susceptibility to opsonophagocytosis, complement deposition, and whole blood survival were characterised for a range of emm types across outbreak and non-outbreak isolates. These findings were translated to murine infection models of GAS. The role of streptolysin in determining disease outcome in vivo was investigated, by using two different clinical lineages: the emergent hypervirulent outbreak emm type 32.2 isolates including the development of an isogenic deletion mutant of streptolysin, that ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 22 Aug 2019 09:33
Last Modified: 01 Sep 2024 18:43
DOI: 10.17638/03043666
Supervisors:
  • Kadioglu, Aras
  • French, Neil
  • Dean, Everett
URI: https://livrepository.liverpool.ac.uk/id/eprint/3043666