C-di-GMP is a ubiquitous bacterial second messenger that regulates a wide range of bacterial physiological processes including biofilm formation, virulence, motility and cell differentiation. Here, we have summarized our current knowledge on the upstream signaling factors and downstream effectors of c-di-GMP in addition to the interaction between c-di-GMP and eukaryotic organisms. New discoveries in these areas have enriched our understanding of the diversity of c-di-GMP signaling pathways and provide important clues for us to explore the roles of c-di-GMP signaling in human pathogens such as Mycobacterium tuberculosis.
