A novel C-di-GMP effector linking intracellular virulence regulon to quorum sensing and hypoxia sensing

Pathogenic bacteria have evolved sophisticated mechanisms to respond and adapt to diverse environmental conditions, especially at the early stage of host-pathogen interaction. Their ability to sense the changes at the infection court and to coordinate virulence gene expression among members, are critical for overwhelming host defense responses and establishing infection. In a recently published paper, we have demonstrated that the Clp of X. campestris pv. campestris (Xcc), is a novel c-di-GMP binding protein. In this addendum, I intend to provide detailed discussion on the role and the mechanism of Clp as a molecular link in connecting Xcc intracellular virulence regulon to quorum sensing and hypoxia sensing, which are two of the important environmental cues that influence the bacterial pathogenicity. In addition, I compare the c-di-GMP effector Clp with its close homologue Crp, which is a well-characterized cAMP receptor, in the context of ligand specificity, mode of action, and their corresponding biological functions. The identification of Clp as a c-di-GMP receptor has provided further understanding how a bacterial pathogen could accommodate and integrate various signal inputs for its benefit. Significantly, this study has also presented solid evidence that Crp-family proteins can be categorized into two functional groups, i.e., cAMP receptor and c-di-GMP effector, based on the corresponding signature amino acid residues in the conserved cNMP binding domain.