Streptococcus gallolyticus subspecies gallolyticus (Sgg) is a member of the group D streptococci that colonises the human gut. Sgg has been long associated with colorectal cancer (CRC), causing bloodstream infections in patients. Streptococcus gallolyticus subspecies pasteurianus (Sgp) and Streptococcus lutetiensis (Sl) are closely related gut pathogens not associated with CRC but also capable of causing bloodstream infections.
We recently identified that Sgg displays twitching motility using a Type IV Pilus (T4P). The presence of a T4P, namely the com pilus, was confirmed through PCR and electron microscopy. Motility in Sgg was significantly inhibited following growth in the presence of excess glucose (p<0.0001). However, Sgp and Sl displayed higher motility and less inhibition in excess sugar compared to Sgg.
Subsequently, invasion by the three species was investigated by infecting CRC cell lines, HT-29 and HCT-116, with bacteria grown in the presence/absence of glucose (0.5%). Again, glucose significantly reduced the invasive capacity of all three species. Interestingly, Sgg invaded HCT-116 more robustly than HT-29, while the opposite was true for Sgp. Importantly, HCT-116 is a more visually dysplastic cell line than HT-29.
Therefore, it is possible that Sgp and Sl invade healthy undamaged mucosa as opposed to Sgg that may require exposed extracellular matrix or basolateral cell receptors which often occur in tumours. Growth conditions that suppress motility also inhibit the ability of Sgg to invade CRC cells. We have carried out comparative genomics to further elucidate the relationship of Sgg with CRC compared to closely related species that lack this interaction.