Table 1 Different types of c-di-GMP receptors from prokaryotes and eukaryotes

Bacteria

Tlp1

Azospirillum brasilense

PilZ domain

-

Promoted persistent motility

[31]

Cbp1

A. caulinodans

PilZ domain

14.94 μM

Regulated motility, biofilm formation, and virulence

[9]

YkuI

Bacillus subtilis

EAL domain

-

-

[32]

YdaK

B. subtilis

GGDEF domain

1.1 µM

-

[33]

YdaK

B. velezensis

GGDEF domain

-

Regulated biofilm formation and bacterial colonization

[34]

PlzA

Borrelia burgdorferi

PilZ domain

6.25 μM

Required to survived within ticks

[35]

PlzB

B. burgdorferi

PilZ domain

0.002 μM

Enhanced biological fitness

[36]

PlzA

B. burgdorferi

PilZ domain

-

Multiple cellular activities were regulated, including osmolality sensing, motility, and nutrition usage

[37]

PlzA

• B. burgdorferi

• B. hermsii

xPliZ domain

6.25 μM

Carried out environment-specific roles in Borreliella biology

[38]

Bcam1349

Burkholderia cenocepacia

GGDEF and EAL domain

10 μM

• Regulated production of cellulose and fimbriae

• Regulated biofilm formation and virulence

[39]

RpfR

B. cenocepacia

EAL domain

2.92 μM

-

[40]

YajQ

B. gladioli

-

-

Mediated endophytic mobility-based defense for host

[41]

PleD

Caulobacter crescentus

DGC domain

-

-

[42]

DgrA

• C. crescentus

• Salmonella Typhimurium

• Pseudomonas aeruginosa

PilZ domain

 < 0.05 μM

Regulated cell motility control

[43]

CbrR

Campylobacter jejuni

-

-

Acted as a virulence factor in the pathogenesis

[44]

PopA

C. crescentus

GGDEF domain

2 μM

Controlled the cell cycle

[45]

ShkA

C. crescentus

Pseudo-receiver domain

-

• TacA transcription factor activation

• Started a G1/S-specific transcription program, resulting in cell morphogenesis and S-phase entry

[46]

TipF

C. crescentus

EAL domain

32.5 μM

Formed polar flagellar assembly

[47]

CckA

C. crescentus

-

4.7 μM

• Inhibited kinase activity

• Stimulated phosphatase activity

[48]

Riboswitch class-II

Clostridium difficile

-

-

Involved in the ribozyme self-splicing

[49]

PilB2

C. perfringens

-

1.34 μM

-

[50]

BcsA

Dickeya oryzae

PilZ domain

0.98 μM

Controlled bacterial biofilm formation

[51]

YcgR

D. oryzae

PilZ domain

-

Modulated the bacterial motility phenotype by increasing putrescine levels

[52]

BcsA

Erwinia amylovora

PilZ domain

-

Activated cellulose biosynthesis

[53]

CsrD

E. amylovora

EAL domain

1.7 μM

Contributed to virulence and biofilm formation

[54]

PNPase

Escherichia coli

-

2.9 μM

Catalyzed phosphorolysis of RNA

[55, 56]

• PgaC

• PgaD

E. coli

-

0.062 μM

Induced biofilm formation

[57]

BcsE

E. coli

GIL and GGDEF I-site-like domain

2.4 μM

Required for maximal cellulose production

[58]

BolA

E. coli

-

-

• Enhanced survivability under various circumstances

• Involved in the production of biofilms

[59]

MrkH

Klebsiella pneumoniae

PilZ and MrkH N domain

0.107 μM

Promoted biofilm formation

[60]

• WspR

• RpfG

Lysobacter enzymogenes

REC domain joined to GGDEF and N-terminal REC domain linked to C-terminal HD-GYP domain

0.15 μM

Regulated biofilm formation

[61]

ArgR

Mycobacterium bovis

-

0.34 μM

Triggered Mycobacterium to adapt to hypoxia through

[62]

LtmA (MSMEG-6479)

M. smegmatis

TetR-type HTH domain

0.83 μM

Regulated cell wall permeability and cell wall composition

[63]

DarR (MSMEG-5346)

M. smegmatis

HTH DNA-binding domain at the N-terminus, QacR-like domain at the C-terminus

2.3 μM

-

[64]

HpoR (MSMEG_5860)

M. smegmatis

-

1.78 μM

Enhanced the mycobacterial H₂O₂ resistance

[65]

• LtmA (MSMEG-6479)

• HpoR (MSMEG_5860)

M. smegmatis

-

• 0.62 μM for LtmA

• 0.29 μM for HpoR

Enhanced bacterial growth under antibiotic-stressful conditions

[66]

DevR

M. smegmatis

C-terminal DNA-binding domain

1.96 μm

Involved in the regulation of mycobacterial oxidative adaptation

[67]

PdtaS

M. tuberculosis

GAF domain

0.33 μM

-

[68]

SgmT

Myxococcus xanthus

GGDEF domain

-

-

[69]

CdbA (MXAN_4361)

M. xanthus

RHH DNA binding domain

 ~ 0.083 μM

Contributed to chromosome organization

[70]

CdbS

M. xanthus

PilZ domain

 ~ 1.4 μM

Heat stress accelerates chromosomal disorganization and cell death

[71]

PilZ

P. aeruginosa

PilZ domain

-

• Produced functional pili

• Biosynthesized exopolysaccharide

• Regulated flagellar motor activity

• Expressed virulence gene

[72,73,74]

Alg44

P. aeruginosa

PilZ domain

-

Biosynthesized alginate

[75,76,77,78]

WspR

P. aeruginosa

GGDEF domain

-

Controlled biofilm formation

[79, 80]

FimX

• P. aeruginosa

• Xanthomonas citri

• X. oryzae pv. oryzae

GGDEF and EAL domain

0.1–0.2 μM

Regulated twitching motility, biofilm formation, and bacterial virulence expression

[18, 81,82,83,84]

PelD

P. aeruginosa

GAF and GGDEF domain

0.5–1.9 μM

Produced Pel polysaccharide

[76, 85]

FleQ

P. aeruginosa

N-terminal FleQ, central AAA + ATPase, and C-terminal HTH DNA-binding domain

7 μM

Down-regulated flagella gene expression

[86]

BrlR

P. aeruginosa

HTH_BrmR and Gyrl-like domain

2.2 μM

Contributed to the high-level drug tolerance of biofilms

[87]

FimX

P. aeruginosa

EAL domain

0.09 μM

Type IV pili assembly and twitching motility are regulated

[88]

FlgZ

P. aeruginosa

PilZ domain

-

Controlled swarming motility

[89]

BrlR

P. aeruginosa

DNA-binding domain

7.3 μM

Mediated antibiotic resistance

[90]

MapZ

P. aeruginosa

PilZ domain

μM

• The flagellar motor switching frequency was reduced

• Surface attachment occurs during biofilm development

[91]

HapZ

P. aeruginosa

PilZ domain

2.0 μM

Mediated bacterial motility and biofilm formation

[10]

LapD

P. fluorescens

EAL domain

5.5–13.1 μM

Required for biofilm development and stable surface adhesion

[92,93,94]

• LapD

• LapG

P. fluorescens

EAL domain

1.9 µM

Controlled cell adhesion and biofilm formation

[95]

YcgR

• S. Typhimurium

• E. coli

PilZ domain

0.18–0.84 μM

Regulated flagellum-based motility

[8, 19, 43, 96]

BcsA

• S. Typhimurium

• E. coli

PilZ domain

8.2 μM

Stimulated bacterial cellulose production

[96, 97]

BgsA

Sinorhizobium meliloti

C-terminal cytoplasmic domain

-

Encoded glycosyl transferase

[98]

CuxR

S. meliloti

Cupin domain

6.7 µM

Induced expression of EPS biosynthesis gene cluster

[99]

SaCpaA_RCK

Staphylococcus aureus

RCK domain

9 μM

Regulated ion transport

[100]

KdpD

S. aureus

USP domain

2 μM

Involved in the control of the two primary K⁺ uptake systems' activity and expression

[101]

FsnR (Smlt2299)

Stenotrophomonas maltophilia

REC and HTH domain

3.43 μM

Elicited flagellar gene expression

[102]

BldD

• Streptomyces coelicolor

• S. venezuelae

-

2.5 μM

Repressed expression of sporulation genes

[25]

BldD

S. ghanaensis

-

-

Played a role in morphological differentiation

[103]

GlgX

S. venezuelae

C-domain

 ~ 8 µM

Stimulated the enzyme's catalytic activity to hydrolyze glycogen

[104]

TDE0214

Treponema denticola

PilZ domain

1.73 μM

Played roles in spirochete motility, biofilm formation, and pathogenicity

[105]

• PlzC (VC_2344)

• PlzD (VCA0042)

Vibrio cholerae

PilZ domain

0.1–0.3 μM

Regulated biofilm formation, motility, and virulence

[106, 107]

VpsT

V. cholerae

REC and HTH domain

3.2 μM

• Promoted biofilm formation

• Down-regulated motility genes

[108]

VpsR

V. cholerae

ATP binding and HTH DNA binding domain

1.6 μM

Controlled biofilm development

[109]

FlrA

V. cholerae

N-terminal receiver, AAA + , and C-terminal DNA-binding domain

0.38 μM

Regulated flagellar biosynthesis

[110]

MshEN

V. cholerae

MshE N-terminal domain

0.014–2 µM

Direct contact with related type II secretion and type IV pili ATPases regulates membrane complexes

[21, 111]

GbpA

V. cholerae

-

-

Attached to environmental and host surfaces containing N-acetylglucosamine moieties

[112]

TfoY

V. cholerae

TfoX N-terminal domain

-

Regulated natural competency, type VI secretion system, and motility

[113]

Riboswitch class-I

V. cholerae

-

-

Helped in RNA compaction and structural rearrangement

[114]

BrpT

V. vulnificus

-

135.4 μM

Enhanced cell-surface adherence

[115]

CLP

X. campestris

-

3.5 μM

Regulated bacterial virulence gene expression

[116]

XC_3703

X. campestris pv. campestris

-

2 µM

Activated virulence-related genes

[117]

• PXO_00049

• PXO_02374

• PXO_02715

X. oryzae pv. oryzae

PilZ domain

• 0.139 μM for PXO_00049

• 0.102 μM for PXO_02374

Regulated virulence

[118]

PilZX3 (PXO_02715)

X. oryzae pv. oryzae

GGDEF amd EAL domain

-

Regulated virulence

[119]

GdpX6 (PXO_02019)

X. oryzae pv. oryzae

GGDEF domain

9 μM

Controlled the virulence, swimming and sliding motility, and biofilm formation

[120]

Cyanobacteria

 CdgR

Anabaena PCC 7120

-

-

Regulated cell size

[121]

 Cellulose synthase Tll0007

Thermosynechococcus vulcanus

PilZ domain

63.9 µM

Being necessary for cell aggregation

[122]

Plants

 atCNTE1

• Arabidopsis thaliana

• Oryza sativa

CNB and GAF domain

-

-

[123]

 Cellulose synthase

Gossypium hirsutum

-

13–24 μM

Involved in cellulose synthesis

[124]

Animal

 LcSTING2

Larimichthys crocea

TMEM173 domain

-

Exhibited immune response against parasites

[125]

 MPYS

Mouse

-

-

Induced cytokine expression

[126]

Other eukaryotes

 P21^ras

Jurkat cells

-

-

Expressed the CD4 receptor

[127]

 STING

HEK293T cells

Amino-terminal domain

 ~ 5.65 μM

• Functioned as immunosensor

• Elicited IFN production

[23, 128, 129]

 Coronin 1A

Mammalian macrophages

Nucleotide-binding domain

-

• Induced IFN-I expression

• Stimulated inflammatory responses

[130]

 Cyclophilin H

Mammalian macrophages

Nucleotide-binding domain

-

• Induced IFN-I expression

• Stimulated inflammatory responses

[130]

 Heliase DDX41

Mouse and human cells

DEAD-box domain

 ~ 5.65 μM

STING triggered the type I IFN host immunological response

[131]

 STING

Drosophila melanogaster

C-terminal domain

-

Initiated innate immune response

[132]