Comparative genomic analysis of the CsoR-family Ni2+/Co2+ regulators

Metals are essential for many cellular processes, yet at excessive levels they are toxic, therefore metal concentrations in a cell must be tightly regulated. In bacteria, such regulation is often carried out by transcription factors (TFs). Here, we use comparative genomics approach to study CsoR-family TFs regulating the Ni 2+ /Co 2+ (nickel and cobalt) homeostasis. We identify binding motifs and reconstruct regulons for the respective TFs. Binding motifs of the studied Ni 2+ /Co 2+ regulators differ, but are all characterized by G/C-rich centers with AT-rich flanks. Most of them are palindromes or inverted repeats conforming to the ATA-N 11 -TAT pattern typical for the CsoR-family TFs. Most regulons are comprised of diverse efflux and influx Ni 2+ /Co 2+ transporters and also often include genes involved in the homeostasis of other metals such as iron, copper, chromium. Important members of studied regulons are genes encoding Fe-S proteins and proteins involved in the biosynthesis of Fe-S clusters, nitrogen metabolism enzymes, SAM-dependent methyltransferases, metalloenzymes, and various transcription factors. Composition of reconstructed regulons for Ni 2+ /Co 2+ CsoR-family TFs demonstrates interconnections in the cell adaptation to different metal stressors and indicates intricate regulatory networks.