Campbell, I. W.; Basta, D. W.; Zingl, F. G.; Sullivan, E. J.; Doranga, S.; Waldor, M. K.

The natural context in which CRISPR-Cas systems are active in Enterobacteriaceae has remained enigmatic. Here, we find that the Citrobacter rodentium Type I-E CRISPR-Cas system is activated by the oxygen-responsive transcriptional regulator Fnr in the anoxic mouse intestine. Since Fnr-dependent regulation is predicted in ~41% of Enterobacteriaceae cas3 orthologs, we propose that anoxic regulation of CRISPR-Cas immunity is an adaptation that protects Enterobacteriaceae against threats arising from the intestinal microbiome.