Characterisation of AspA, an AgI/II-family protein in Streptococcus pyogenes

Streptococcus pyogenes or Group A Streptococcus (GAS) is a human pathogen capable of causing a wide array of severe and lethal diseases and accounts for over half a million deaths a year globally. A major problem that exists in treating S. pyogenes infections is high rates of disease recurrence and treatment failure which could lead to more severe infections. Existence of S. pyogenes in biofilm structures has been suggested to contribute to the rates of recurrent infections, as biofilms have been shown to contribute to the ability of an organism to evade immune responses and impart resistance to chemical and mechanical stresses. Integral components of biofilms of many bacterial species are functional amyloid fibres, which are thought to act as a scaffold within biofilms to provide structure and stability through the nature of the biophysical properties of amyloid fibres. In this thesis, the function of AspA as a protein component of biofilms is investigated. AspA is a surface anchored AgI/II family adhesin in S. pyogenes, which we hypothesised to be able to form functional amyloid fibres in S. pyogenes biofilm. Through in vitro biophysical tests on recombinant protein and studies of S. pyogenes biofilm culture this hypothesis is tested. In the latter part of this thesis, the prevalence and diversity of AspA and other AgI/II proteins in a global population of S. pyogenes isolates is interrogated bioinformatically.