The human gut bacterial genotoxin colibactin alkylates DNA

Bacterial warhead targets DNA The bacterial toxin colibactin causes double-stranded DNA breaks and is associated with the occurrence of bacterially induced colorectal cancer in humans. However, isolation of colibactin is difficult, and its mode of action is poorly understood. Wilsonet al. studiedEscherichia coli that contain the biosynthetic gene island calledpks , which is associated with colibactin production (see the Perspective by Bleich and Arthur). They identified the DNA adducts that resulted from incubatingpks + E. coli in human cells. To overcome the lack of colibactin for direct analysis, mimics of thepks product were synthesized. From the resulting synthetic adenine-colibactin adducts, it became evident that alkylation via a cyclopropane “warhead” breaks the DNA strands. Similar DNA adducts were then identified in the gut epithelia of mice infected withpks + E. coli. Science , this issue p.eaar7785 ; see also p.689