Sustained sensing as an emerging principle in second messenger signaling systems

Bacteria utilize a diverse set of nucleotide second messengers to regulate cellular responses by binding macromolecular receptors (RNAs and proteins). Recent studies on cyclic di-GMP (c-di-GMP) have shown that this signaling molecule binds multiple receptors to regulate different steps in the same biological process. We propose this property of the same molecule regulating multiple steps in the same process is biologically meaningful and have termed this phenomenon 'sustained sensing'. Here, we discuss the recent findings that support the concept of sustained sensing of c-di-GMP levels and provide additional examples that support the utilization of sustained sensing by other second messengers. Sustained sensing may be widespread in bacteria and provides an additional level of complexity in prokaryotic signal transduction networks.