Elucidating the role of colibactin in pks+ associated mutagenesis using stable synthetic analogs

In this study, we investigate host response to colibactin 742 , and the related gem-dimethyl derivative (colibactin 746, which is incapable of generating DNA ICLs) at the level of global gene regulation and somatic mutation using intestinal epithelial cells. We identified unique host-response pathways activated in a time- and dose-dependent fashion, and showed that chronic synthetic colibactin exposure alters host transcriptional and genomic landscapes in a manner similar to pks E. coli. These data suggest that colibactin is the causual agent underlying pks-associated mutagenesis.