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

Abstract

EMBO J 32 18, 2430–2438 doi:; DOI: 10.1038/emboj.2013.165; published online July 23 2013

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.

Figure 1

Major cGMP receptors in bacterial and eukaryotic cells. The cGMP-specific cNMP-binding domains (PF00027 in Pfam) are present in both eukaryotes and bacteria. In eukaryotes, major cGMP receptors include protein kinases; cyclic nucleotide-gated ion channels and cNMP phosphodiesterases. In bacteria, the newly characterized cNMP–GGDEF domain fusion protein XC_0249 (UniProt entry Q4V037_XANC8) synthesizes c-di-GMP under the control of cGMP. Other potential cGMP targets include a likely cNMP-regulated ion channel BBta_5447 from Bradyrhizobium sp. (UniProt: A5EML8_BRASB, contains the PF00520 domain), protein serine phosphatase Cagg_2419 from Chloroflexus aggregans (UniProt: B8G3B9_CHLAD, contains the PP2C or SpoIIE domain, PF07228) and Rhodospirillum centenum transcriptional regulator RC1-3788 (Marden et al, 2011).