Abstract
Streptococcus gallolyticus, subspecies gallolyticus (Sgg) is a gram-positive bacterium associated with infective endocarditis and colorectal cancer (CRC). Sgg has features that allow the bacterium to thrive in the colorectal tumor microenvironment and further progress the development of CRC to facilitate its survival. Sgg contains 3 pili that facilitate colonic cell adhesion and translocation through phase variation. Sgg also contains bile salt hydrolase and a bacteriocin called gallocin with substantially increased activity in bile acids, which facilitates its growth in the bile acid-rich adenomatous colorectal microenvironment. Sgg also uses tumor metabolites as an energy source. Sgg also possesses tannase, which metabolizes gallotannin to be used as a carbon source and reduces the anti-apoptotic effects of tannins, driving CRC progression. Sgg also interferes with a variety of oncogenic cell signaling pathways, including the Wnt/β-catenin pathway through mechanisms that are not fully elucidated. Increased β-catenin signaling also enhances adhesion via increased expression of the extracellular matrix and increases bile acid concentrations in the lumen through downregulation of an apical bile acid transporter. Finally, Sgg induces biotransformation of toxic substrates in CRC cells, which leads to formation of toxic intermediates and DNA adducts, promoting further progression of CRC.