c-di-GMP-induced conformational dynamics of the c-di-GMP-binding protein A (CdbA) from Myxococcus xanthus

The second messenger c-di-GMP has important functions in response to changing environmental and cellular cues in bacteria. Here, we report the identification of CdbA, a DNA binding protein of the ribbon-helix-helix family in Myxococcus xanthus, and show that it binds c-di-GMP in vitro. CdbA is essential for viability and its depletion caused defects in chromosome organization and segregation resulting in a block in cell division. CdbA binds multiple sites across the M. xanthus genome with moderate sequence specificity; however, its depletion only caused minor changes in transcription. C-di-GMP binding and DNA binding by CdbA are mutually exclusive and substitutions in the CdbA interfaces important for c-di-GMP binding not only abolished c-di-GMP binding but also DNA binding and rendered the mutant proteins non-functional in vivo. Our data are consistent with a model whereby CdbA functions as a nucleoid associated protein to organize the M. xanthus chromosome and the function of CdbA is modulated by c-di-GMP, thus, for the first time, establishing a link between c-di-GMP and chromosome organization and segregation.