A Cyclic di-GMP Network Is Present in Gram-Positive Streptococcus and Gram-Negative Proteus Species.

Ying Liu,Changhan Lee,Fengyang Li,Roman Zubarev,Rey-Ting Guo,Janja Trček,Alexey Chernobrovkin,Chun-Chi Chen,Ute Römling,Heike Bähre

doi:10.1021/acsinfecdis.0c00314

Abstract

The ubiquitous cyclic di-GMP (c-di-GMP) network is highly redundant with numerous GGDEF domain proteins as diguanylate cyclases and EAL domain proteins as c-di-GMP specific phosphodiesterases comprising those domains as two of the most abundant bacterial domain superfamilies. One hallmark of the c-di-GMP network is its exalted plasticity as c-di-GMP turnover proteins can rapidly vanish from species within a genus and possess an above average transmissibility. To address the evolutionary forces of c-di-GMP turnover protein maintenance, conservation, and diversity, we investigated a Gram-positive and a Gram-negative species, which preserved only one single clearly identifiable GGDEF domain protein. Species of the family Morganellaceae of the order Enterobacterales exceptionally show disappearance of the c-di-GMP signaling network, but Proteus spp. still retained one diguanylate cyclase. As another example, in species of the bovis, pyogenes, and salivarius subgroups as well as Streptococcus suis and Streptococcus henryi of the genus Streptococcus, one candidate diguanylate cyclase was frequently identified. We demonstrate that both proteins encompass PAS (Per-ARNT-Sim)-GGDEF domains, possess diguanylate cyclase catalytic activity, and are suggested to signal via a PilZ receptor domain at the C-terminus of type 2 glycosyltransferase constituting BcsA cellulose synthases and a cellulose synthase-like protein CelA, respectively. Preservation of the ancient link between production of cellulose(-like) exopolysaccharides and c-di-GMP signaling indicates that this functionality is even of high ecological importance upon maintenance of the last remnants of a c-di-GMP signaling network in some of today’s free-living bacteria.

Highlights

The ubiquitous cyclic di-GMP (c-di-GMP) network is highly redundant with numerous GGDEF domain proteins as diguanylate cyclases and EAL domain proteins as c-di-GMP specific phosphodiesterases comprising those domains as two of the most abundant bacterial domain superfamilies
Network reduction on a short evolutionary time scale is exemplified in the human pathogens Shigella spp. and Yersinia pestis, which, in contrast to their close relatives E. coli and Yersinia enterocolitica, possess a highly reduced c-di-GMP network.[2,30]
Cyclic di-GMP signaling systems of species of the type genera Escherichia, Erwinia, Yersinia, and Dickeya of the four first families, which usually possess a high density of c-di-GMP turnover proteins, have been well investigated.[2]

Summary

Introduction

The ubiquitous cyclic di-GMP (c-di-GMP) network is highly redundant with numerous GGDEF domain proteins as diguanylate cyclases and EAL domain proteins as c-di-GMP specific phosphodiesterases comprising those domains as two of the most abundant bacterial domain superfamilies. Species of the family Morganellaceae of the order Enterobacterales exceptionally show disappearance of the c-di-GMP signaling network, but Proteus spp. still retained one diguanylate cyclase As another example, in species of the bovis, pyogenes, and salivarius subgroups as well as Streptococcus suis and Streptococcus henryi of the genus Streptococcus, one candidate diguanylate cyclase was frequently identified. The GG(D/E)EF domain synthesizes c-di-GMP in a two-step reaction with 5′-pppGpG as an intermediate and two molecules of pyrophosphate as byproducts.[3] The EAL- and HD-GYP domains hydrolyze c-di-GMP into linear 5′-pGpG and GMP, respectively.[4,5] Numerous proteins are bifunctional through a combination of GGDEF with EAL/HD-GYP domains In these three superfamilies, catalytic domains have evolved into receptors or act though protein−protein interactions.[6] an intact GG(D/E)EF motif is usually an indicator for catalytic activity, due to the requirement of extended consensus motifs, the presence of such a motif and even the presence of extended consensus signature motif(s), including ligands binding divalent ion required for catalytic activity, is not a guarantee for catalytic activity[7,8] or substrate specificity[9,10] and vice versa.[11,12]

Methods

Results

Conclusion