The synthesis of the novel Escherichia coli toxin—colibactin and its mechanisms of tumorigenesis of colorectal cancer Original paper

What was reviewed?

This mini-review explained how the pks gene cluster in E. coli B2 strains produces the genotoxin colibactin and how that toxin contributes to colorectal cancer (CRC). The authors emphasized that colibactin is structurally unstable and hard to isolate, so researchers infer its biosynthesis and activity from genetics, enzymology, chemical synthesis, and DNA-alkylation studies, then connect those mechanistic insights to CRC-relevant outcomes such as genomic instability, barrier disruption, and tumor promotion.

Who was reviewed?

Because this was a review, it synthesized findings across experimental and clinical contexts rather than enrolling a single cohort. It relied heavily on studies using human epithelial systems (including organoid lumen microinjection) to define colibactin-associated mutation patterns, and on mouse models of inflammation and colon tumorigenesis where pks-positive bacteria induce DNA damage and accelerate tumor development, framing these results as biologically plausible mechanisms that can operate in the human colon.

What were the most important findings?

For a microbiome signatures database, the key major microbial association is functional: colonization or local enrichment with pks-positive (colibactin-producing) Enterobacteriaceae, especially E. coli B2, signals potential genotoxic pressure in the colon. The review described a stepwise biosynthetic model in which the clb-encoded PKS/NRPS machinery generates precolibactin, ClbM transports intermediates into the periplasm, and ClbP cleaves a prodrug motif to release active colibactin, while resistance mechanisms protect the bacterium. Mechanistically, the authors highlighted DNA injury patterns that strengthen causal attribution: exposure to pks-positive bacteria increases single-base substitutions, produces a characteristic small indel footprint often called ID-pks (notably single T deletions in T homopolymers), and induces interstrand crosslinks that can progress to double-strand breaks, creating a credible pathway from microbial genotype to colorectal carcinogenesis.

What are the greatest implications of this study/ review?

This review supports using pks/clb detection as a clinically meaningful microbiome marker in CRC-relevant settings because it links a defined microbial gene island to specific DNA damage mechanisms and recognizable mutational footprints rather than to nonspecific dysbiosis. It also points to practical intervention logic: instead of focusing only on eradicating the organism, clinicians and translational teams can target toxin production and release steps—especially the maturation step required for active colibactin—and consider host-context levers that can shift genotoxic output, because changes in the intestinal microenvironment can plausibly amplify or dampen toxin activity and therefore modify risk.