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

Abstract

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 signaltransduction 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. In higher eukaryotes, cAMP and cGMP are important second messengers that mediate effects of light, nitric oxide, hormones and other signals to regulate vision, muscle contraction, vasodilatory effects, sleep, memory and various other functions, see, for example, Beavo and Brunton (2002). Over the last half of a century, studies of cAMP- and cGMPrelated systems have been rewarded with six Nobel prizes in Physiology or Medicine and one in Chemistry. In all eukaryotes, synthesis of cAMP and cGMP is catalysed by similar enzymes that belong to the class III adenylate/ guanylate cyclase family (PF00211 in the Pfam database,