Streptococcus gallolyticus gallolyticus pathogenicity (360G-Wellcome-109163_Z_15_A)
Streptococcus gallolyticus is a gram positive gut commensal that can cause Infective endocarditis (IE) a heart valve infection. Unusually, in the case of S. gallolyticus, patients presenting with infective endocarditis are also found to have colonic abnormalities i.e. colorectal cancer. It is thought that the presence of colorectal cancer allows translocation of the pathogen from the gut lumen into the bloodstream. To date, there is limited information on the virulence factors of S. gallolyticus that contribute to the pathogenesis of IE. This study aims to (1) identify common virulence factors in clinical isolates of S. gallolyticus from bloodstream infections and IE. This will be achieved by sequencing and de novo assembly of the genomes of 50 clinical isolates from Ireland, France, Italy, Spain and the US. The relatedness of these strains will be analysed and virulence factors identified. (2) Genes encoding these virulence factors will be deleted and the ability of the mutant strains to adhere to platelets, trigger platelet aggregation and adhere to colonic epithelial cells will be tested. (3) These genes will also be cloned into expression vectors and expressed in a surrogate expression host to analyse any gain of function conferred.
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