Cyclic di-GMP (also called cyclic diguanylate and c-di-
GMP) is a
second messenger used in signal transduction in a wide variety of
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
.
Cyclic di-GMP is not known to be used by
archaea
Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...
, and has only been observed in
eukaryotes in ''
Dictyostelium''.
The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in ''
Gluconacetobacter xylinus'' in order to produce
microbial cellulose.
In structure, it is a cycle containing only two
guanine
Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...
bases linked by
ribose and
phosphate
Phosphates are the naturally occurring form of the element phosphorus.
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
.
Function
Contact with surfaces increases c-di-GMP which increases
transcription,
translation, and
post translation of
exopolysaccharides (EPSs) and other
extracellular polymeric substance
Extracellular polymeric substances (EPS) are biopolymer, natural polymers of molecular mass, high molecular weight secreted by microorganisms into their environment. EPS establish the functional and structural integrity of biofilms, and are consid ...
matrix components (see the review by Jenal et al 2017).
In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s with
diguanylate cyclase activity. These proteins typically have a characteristic
GGDEF motif, which refers to a conserved sequence of five
amino acids. Degradation of cyclic di-GMP is affected by proteins with
phosphodiesterase activity. These proteins have either an EAL or an HD-GYP amino acid motif. Processes that are known to be regulated by cyclic di-GMP, at least in some organisms, include
biofilm
A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...
formation (such as EPS matrices found by Steiner et al 2013),
motility
Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components.
Motility is observed in ...
(especially the motile-to-sessile transition, see the review by Jenal et al 2017)
and
virulence factor production.
Regulation
Cyclic di-GMP levels are regulated using a variety of mechanisms. Many proteins with GGDEF,
EAL or HD-GYP domains are found with other domains that can receive signals, such as
PAS domains. Enzymes that degrade or synthesize cyclic di-GMP are believed to be localized to specific regions of the cell, where they influence receivers in a restricted space.
In ''Gluconacetobacter xylinus,'' c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase.
Some diguanylate cyclase enzymes are allosterically inhibited by cyclic di-GMP.
Cyclic di-GMP levels regulate other processes via a number of mechanisms. The ''Gluconacetobacter xylinus'' cellulose synthase is allosterically stimulated by cyclic di-GMP, presenting a mechanism by which cyclic di-GMP can regulate cellulose synthase activity. The PilZ domain has been shown to bind cyclic di-GMP and is believed to be involved in cyclic di-GMP-dependent regulation, but the mechanism by which it does this is unknown. Recent structural studies of PilZ domains from two bacterial species have demonstrated that PilZ domains change conformation drastically upon binding to cyclic di-GMP. This leads to the strong inference that conformational changes in PilZ domains allow the activity of targeted effector proteins (such as cellulose synthase) to be regulated by cyclic di-GMP.
Riboswitches called the
cyclic di-GMP-I riboswitch and
cyclic di-GMP-II riboswitch regulate gene expression in response to cyclic di-GMP concentrations in a variety of bacteria, but not all bacteria that are known to use cyclic di-GMP.
Host-association
Cyclic di-GMP has been linked to host-association in multiple ''Pseudomonas'' species. In an experiment where ''Pseudomonas lurida'' was grown in association with the nematode host ''Caenorhabditis elegans'' genetic mutations were observed in certain genes that upregulated c-di-GMP, causing a host specialist morphotype to emerge. The mutations affecting c-di-GMP regulation were uncovered with whole genome sequencing. Genes ''wspE'' and ''wspF'' from the wsp operon exhibited mutations that upregulated c-di-GMP. Additionally, mutations in the gene ''rph'' were determined to also affect c-di-GMP expression, which is a novel discovery because ''rph'' has not previously been linked to c-di-GMP regulation.
For a review of c-di-GMP roles in ''
Caulobacter crescentus'', ''
Pseudomonas aeruginosa'', ''
Komagataeibacter xylinus''/''Gluconacetobacter xylinus'', ''
Myxococcus xanthus'', ''
Bdellovibrio bacteriovorus'' and ''
Pseudomonas fluorescens'' see Jenal et al 2017.
See also
*
Cyclic di-AMP
References
{{DEFAULTSORT:Cyclic Di-Gmp
Nucleotides
Cyclic nucleotides