We investigate the molecular basis for the subversion of host cell signalling and uptake processes by Streptococcus pyogenes and the autoimmune response triggered by some streptococcal infections. This remarkably versatile and important human pathogen causes a wide range of diseases including pharyngitis, impetigo, glomerulonephritis, rheumatic heart disease, necrotising fasciitis and toxic shock syndrome. The conservative estimate of 500000 deaths per annum places Streptococcus pyogenes among the major human pathogens (WHO report 2004). The complex pathogenicity of streptococci is reflected by the expression of a multitude of virulence factors. We currently focus on three cell-wall anchored proteins, SfbI, FbaB and the M protein. These proteins play a role in the persistence of streptococcal infections, invasive infections and the development of rheumatogenic sequelae, respectively. We use a range of biophysical techniques, most importantly NMR spectroscopy and microcalorimetry, to understand the structures and molecular interactions of these bacterial virulence factors with human proteins. Ultimately, this research will contribute to the development of new strategies that are needed to tackle the enormous health burden of streptococcal diseases.
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