Warner David Michael, Mehta Arunab Harish
University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Hospital Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
Gut Microbiome (Camb). 2024 Nov 4;5:e9. doi: 10.1017/gmb.2024.11. eCollection 2024.
, subspecies (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.
亚种(Sgg)是一种革兰氏阳性菌,与感染性心内膜炎和结直肠癌(CRC)相关。Sgg具有一些特性,使其能够在结直肠癌肿瘤微环境中茁壮成长,并进一步推动CRC的发展以促进其存活。Sgg含有3种菌毛,可通过相变促进结肠细胞黏附和易位。Sgg还含有胆盐水解酶和一种名为gallocin的细菌素,其在胆汁酸中的活性大幅增加,这有助于其在富含胆汁酸的腺瘤性结直肠微环境中生长。Sgg还利用肿瘤代谢物作为能量来源。Sgg还拥有鞣酸酶,可将没食子鞣酸代谢为碳源,并降低单宁的抗凋亡作用,从而推动CRC进展。Sgg还会干扰多种致癌细胞信号通路,包括Wnt/β-连环蛋白通路,但其具体机制尚未完全阐明。β-连环蛋白信号的增加还会通过增加细胞外基质的表达来增强黏附,并通过下调顶端胆汁酸转运体来增加肠腔内胆汁酸的浓度。最后,Sgg诱导CRC细胞中毒性底物的生物转化,导致毒性中间体和DNA加合物的形成,促进CRC的进一步进展。