Colibactin

Colibactin is a potent genotoxic secondary metabolite produced by certain strains of Escherichia coli and other Enterobacteriaceae that harbor the pks genomic island (Nature, 2006). It is a complex polyketide-nonribosomal peptide hybrid that induces DNA damage in host intestinal epithelial cells by forming interstrand crosslinks and alkylating DNA at specific adenine residues (Science, 2019). This damage results in double-strand breaks, chromosomal aberrations, and cell cycle arrest, which are strongly associated with the initiation and progression of colorectal cancer (Nature, 2020). While colibactin itself is a toxin rather than a traditional protein target, its biosynthetic machinery—specifically the peptidase ClbP—is a major focus for therapeutic intervention to prevent its production (Journal of the American Chemical Society, 2016). Furthermore, the identification of a specific mutational signature (SBS88) in human colorectal tumors provides a biomarker for past colibactin exposure (Nature, 2020). Efforts to mitigate colibactin's effects include the development of small-molecule inhibitors of the pks pathway and the use of probiotics to displace pks+ bacteria (Gastroenterology, 2021).

Other names

pks genotoxinpks-derived genotoxin

Colibactin functions as a DNA-alkylating agent that forms interstrand crosslinks, leading to double-strand breaks and genomic instability in host epithelial cells (Science, 2019; Nature, 2020).