Colibactin Explained

Colibactin is a genotoxic metabolite produced by Escherichia coli and other Enterobacteriaceae ("enteric bacteria") believed to cause mutations leading to colorectal cancer and the progression of colorectal cancer.^{[1] [2] [3] [4]} Colibactin is a polyketide peptide that can form interstrand crosslinks in DNA. Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (pks) or clb biosynthetic gene cluster. About 20% of humans are colonized with E. coli that harbor the pks island.^[5]

Colibactin forms DNA inter-strand cross-links by alkylation of adenine moieties on opposing DNA strands. It induces lytic development in certain bacteria that contain prophages.^[6]

Notes and References

1. Arthur JC . Microbiota and colorectal cancer: colibactin makes its mark . . 17 . 6 . 317–318 . 2020. 10.1038/s41575-020-0303-y . 32317778. 216033220 .
2. Zhou T, Hirayama Y, Watanabe K . Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative . . 143 . 14 . 5526–5533 . 2021 . 10.1021/jacs.1c01495 . 33787233. 232431632 .
3. Helmink BA, Khan M, Wargo JA. The microbiome, cancer, and cancer therapy . . 25 . 3 . 377–388. 2019 . 10.1038/s41591-019-0377-7 . 30842679. 71145949 .
4. Wernke KM, Xue M, Herzon SB . Structure and bioactivity of colibactin . . 30 . 15 . 127280 . 2020 . 10.1016/j.bmcl.2020.127280 . 7309967 . 32527463.
5. Balskus EP . Colibactin: understanding an elusive gut bacterial genotoxin . Natural Product Reports . 32 . 11 . 1534–40 . 2015 . 26390983 . 10.1039/c5np00091b .
6. Silpe . Justin E. . Wong . Joel W. H. . Owen . Siân V. . Baym . Michael . Balskus . Emily P. . 2022-02-23 . The bacterial toxin colibactin triggers prophage induction . Nature . 603 . 7900 . en . 315–320 . 10.1038/s41586-022-04444-3. 35197633 . 8907063 . 2022Natur.603..315S . 1476-4687.