Variations among Streptococcus gallolyticus subsp gallolyticus strains in connection with colorectal cancer

Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been reported to display a strong association with colorectal cancer (CRC). It was recently demonstrated to actively promote the development of CRC, underscoring the importance of Sg in both clinical correlation and functional relevance in CRC. Here we investigated several clinical isolates of Sg in their interactions with human colon cancer cells and in mouse models. Some Sg strains were able to stimulate host cell proliferation (proliferationpromoting Sg, PP-Sg) whereas others were not (non-proliferation-promoting Sg, NP-Sg). PP-Sg strains adhered to colon cancer cells much better than NP-Sg strains, suggesting that close contact between Sg and host cells is important. In mice, PP-Sg is significantly better at colonizing the colon tissues of A/J mice compared to NP-Sg, however this difference was not observed in C57BL/6 mice, suggesting that Sg colonization of mouse colon tissues involves specific interactions between bacterial and host factors on the colonic epithelium. Finally, in an azoxymethane-induced mouse model of CRC, PP-Sg promoted tumor development whereas NP-Sg did not. These findings provide clues to the mechanism underlying the Sg-CRC association and have important implications to clinical studies that aim to correlate Sg with clinical and pathological features of CRC.