|Abstract : Group A streptococcus infections are responsible for more than half a million deaths worldwide per year. The bacteria is capable of causing a wide variety of diseases, ranging from superficial, self-limiting infections such as pharyngitis and impetigo to severe, invasive diseases such as toxic shock syndrome and necrotising fasciitis with high mortality. Such diversity is due to a vast array of secreted and surface-expressed virulence factors such as DNases, exotoxins or superantigens although no clear link between specific virulence factors and diseases manifestations has been established to date.
Virulence factors play a variety of roles during infection, including adhesion to host cells, invasion and spread to deeper tissues, break down of those tissues and evasion of the host immune response but the precise underlying molecular mechanisms allowing invasive disease establishment remain poorly characterised. Interestingly, we have obtained a highly necrotising clinical isolate, whose in depth analysis, by in silico, in vitro and in vivo approaches, can allow further elucidation of the specific roles of virulence factors during the establishment of GAS disease.
Our principal objective is to investigate the contribution of a number of GAS proteins to virulence and pathogenesis of invasive Group A Streptococcus disease
using this isolate. Genomic and proteomic analysis of the strain will be performed in conjunction with manipulation of the bacteria both in vivo and in vit|