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.[2] Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (pks)[1] or clb biosynthetic gene cluster.[4] 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.[4] It induces lytic development in certain bacteria that contain prophages.[6]
References
- ^ a b Arthur JC (2020). "Microbiota and colorectal cancer: colibactin makes its mark". Nature Reviews Gastroenterology & Hepatology. 17 (6): 317–318. doi:10.1038/s41575-020-0303-y. PMID 32317778. S2CID 216033220.
- ^ a b Zhou T, Hirayama Y, Watanabe K (2021). "Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative". Journal of the American Chemical Society. 143 (14): 5526–5533. doi:10.1021/jacs.1c01495. PMID 33787233. S2CID 232431632.
- ^ Helmink BA, Khan M, Wargo JA (2019). "The microbiome, cancer, and cancer therapy". Nature Medicine. 25 (3): 377–388. doi:10.1038/s41591-019-0377-7. PMID 30842679. S2CID 71145949.
- ^ a b c Wernke KM, Xue M, Herzon SB (2020). "Structure and bioactivity of colibactin". Bioorganic & Medicinal Chemistry Letters. 30 (15): 127280. doi:10.1016/j.bmcl.2020.127280. PMC 7309967. PMID 32527463.
- ^ Balskus EP (2015). "Colibactin: understanding an elusive gut bacterial genotoxin". Natural Product Reports. 32 (11): 1534–40. doi:10.1039/c5np00091b. PMID 26390983.
- ^ 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): 315–320. Bibcode:2022Natur.603..315S. doi:10.1038/s41586-022-04444-3. ISSN 1476-4687. PMC 8907063. PMID 35197633.