Bacterial second messengers, cGMP and c-di-GMP, in a quest for regulatory dominance

Bacteria and eukaryotes differ in the organization of their key signal-transduction pathways but share certain signalling components, including cyclic nucleotide second messengers. In this issue, a paper by British, Irish and Taiwanese scientists (An et al, 2013) describes a signal-transduction pathway that regulates virulence and biofilm formation in the bacterial plant pathogen Xanthomonas campestris. Remarkably, this pathway involves a cascade of two nucleotide second messengers, with cyclic GMP (cGMP), a typically eukaryotic messenger, directly regulating synthesis of cyclic dimeric GMP (c-di-GMP), a ubiquitous bacterial messenger. This study broadens the scope of cGMP-regulated processes in bacteria, offers structural insights into cGMP binding by bacterial cGMP receptors, and expands the range of bacteria using cGMP in signal transduction. Such multi-level regulatory cascades may well function in other organisms.