Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization

Abstract

Colonization by subsp. (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial steps that explain how CRC favors SGG colonization. By using mice genetically prone to CRC, we show that SGG colonization is 1,000-fold higher in tumor-bearing mice than in normal mice. This selective advantage occurs at the expense of resident intestinal enterococci. An SGG-specific locus encoding a bacteriocin ("gallocin") is shown to kill enterococci in vitro. Importantly, bile acids strongly enhance this bacteriocin activity in vivo, leading to greater SGG colonization. Constitutive activation of the Wnt pathway, one of the earliest signaling alterations in CRC, and the decreased expression of the bile acid apical transporter gene , as an effect of the founding mutation, may thereby sustain intestinal colonization by SGG. We conclude that CRC-specific conditions promote SGG colonization of the gut by replacing commensal enterococci in their niche.

Secretion, maturation and activity of a quorum-sensing peptide (GSP) inducing bacteriocins transcription inStreptococcus gallolyticus

“…S1). The predicted 24-mer GSP was shown 9 to activate transcription of the gallocin genes (Proutière et al, accompanying paper). Therefore, 10 we chemically synthesized GSP 21-mer and GSP 24-mer peptides to test their efficiency in 11 activating gallocin gene transcription.…”

Heterogeneous expression of Pil3 pilus is critical for Streptococcus gallolyticus translocation across polarized colonic epithelial monolayers

“…Sgg is described as a weak colonizer of the 119 the gastrointestinal tract with a fecal carriage of about 2.5 to 15%. It is believed that under 120 certain specific physiological conditions such as development of colon malignancies, Sgg is able 121 to overgrow by benefiting from specific tumoral nutrients and outcompeting closely related 122 microbiota gut commensals (7,8). This increase in Sgg load and the changes in the gut 123 intestinal barrier resulting from tumor development are suspected to favor Sgg translocation 124 across the tight intestinal barrier, which in turn can lead to invasive infections such as septicemia 125…”

“…This Gram-positive coccus is one of the few 5 intestinal bacteria that have been consistently linked to colorectal cancer (CRC) over the last 40 6 years (3) and a recent study confirms this suspicion (4). Whether Sgg is a driver and/or 7 passenger of CRC is the subject of recent studies and evidence for both models have been 8 obtained experimentally (5)(6)(7)(8)(9)(10). 9…”

Decrypting the communication between microbes and the intestinal mucosa—A brief review on Pathogénie Microbienne Moléculaire's latest research

“…Dysbiosis could be directly or indirectly responsible for disease onset by providing a suitable environment for the growth of pathobionts or opportunistic pathogens. Aymeric et al () reported an example for such interactions in the context of intestinal tumourigenesis conferring growth advantage to the opportunistic pathogen S . gallolyticus .…”