The human gut bacterial genotoxin colibactin alkylates DNA
Certain Escherichia coli strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated in colorectal cancer pathogenesis. However, colibactin’s chemical structure and the molecular mechanism underlying its genotoxic effects have remained unknown for more than a decade. Here we combine an untargeted DNA adductomics approach with chemical synthesis to identify and characterize a covalent DNA modification from human cell lines treated with colibactin-producing E. coli. Our data establish that colibactin alkylates DNA with an unusual electrophilic cyclopropane. We show that this metabolite is formed in mice colonized by colibactin-producing E. coli and is likely derived from an initially formed, unstable colibactin-DNA adduct. Our findings reveal a potential biomarker for colibactin exposure and provide mechanistic insights into how a gut microbe may contribute to colorectal carcinogenesis.
Source: ScienceNOW - Category: Science Authors: Wilson, M. R., Jiang, Y., Villalta, P. W., Stornetta, A., Boudreau, P. D., Carra, A., Brennan, C. A., Chun, E., Ngo, L., Samson, L. D., Engelward, B. P., Garrett, W. S., Balbo, S., Balskus, E. P. Tags: Microbiology, Molecular Biology, Online Only r-articles Source Type: news
More News: Biology | Cancer | Cancer & Oncology | Chemistry | Colorectal Cancer | Gastroenteritis | Microbiology | Molecular Biology