Revealing a Microbial Carcinogen

The microbiota in the human gastrointestinal system is predicted to produce hundreds of unique small molecules and secondary metabolites that may influence host health and disease ( 1 ). Many such molecules are produced by sophisticated multienzymatic assembly lines that are encoded by bacterial biosynthetic gene clusters. One class of molecules, colibactins, are produced from the gene cluster called the polyketide synthase ( pks ) island. The pks island occurs in certain strains of Escherichia coli and is prevalent in the microbiota of colorectal cancer (CRC) patients ( 2 – 5 ). However, despite more than a decade of research into the potential carcinogenic role of colibactin, little is known about its structure or mechanism of action. On page 709 of this issue, Wilson et al. ( 6 ) show that colibactin alkylates DNA in cultured cells and in vivo, forming covalent modifications known as DNA adducts. These colibactin-DNA adducts are chemical evidence of DNA damage and represent a detectable signature of exposure to colibactin. Misrepaired DNA adducts may generate mutations that contribute to colorectal tumorigenesis.