Abstract
Commensal and extra-intestinal pathogenic strains of E. coli frequently harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. The gut and infected tissue are low oxygen environments, but it is not known whether oxygen modulates production of the genotoxin. Here, we report on the serendipitous observation that oxygenation of the bacterial culture strongly modulates the autotoxicity of a E. coli pks clbS mutant deficient for colibactin self-protection system. We further found that DNA damaging activity by pks+ E. coli decreased with increasing oxygen concentration in the medium. Similarly, the level of the N-myristoyl-D-Asn metabolite that is released during the final step of colibactin synthesis decreased with increasing oxygen concentration. The activity of the promoter of a gene for the colibactin synthase ClbB, as well as its transcription, were maximal under anoxic conditions, but decreased with increased oxygen concentration. Thus, colibactin synthesis is inhibited by oxygen, suggesting that the pks biosynthetic pathway is adapted to the anoxic intestinal lumen and to the hypoxic infected or tumor tissue.
Competing Interest Statement
The authors have declared no competing interest.