KEGG   PATHWAY: paer02025
Entry
paer02025                   Pathway                                
Name
Biofilm formation - Pseudomonas aeruginosa - Pseudomonas aeruginosa PA1R
Description
Surface colonization and subsequent biofilm formation and development provide numerous advantages to microorganisms. The main key actors relevant in the regulation of biofilm formation by Pseudomonas aeruginosa include cAMP/Vfr signaling, quorum sensing (QS) systems, Gac/Rsm pathway, and c-di-GMP signaling. cAMP/Vfr signaling regulates the transcription of hundreds of genes encoding diverse virulence factors, including the type 2 secretion system and type 3 secretion system and their associated toxins, type IV pili, and flagella. It is demonstrated that the accumulation of cAMP inhibits the attachment phase of biofilm formation. The QS systems are arranged hierarchically with the las system positively regulating both the rhl and PQS systems. These three QS systems are involved in the regulation of virulence factor production, biofilm maturation, and motility phenotypes. GacS/GacA two-component system is promoting the expression of two small regulatory RNAs, RsmY and RsmZ, which sequester the translational repressor RsmA. Titration of RsmA induces the production of sessile and biofilm determinants, whereas free RsmA leads to a planktonic and more virulent lifestyle. c-di-GMP is a ubiquitous bacterial second messenger. Synthesis and degradation of c-di-GMP is facilitated by diguanylate cyclases (DGC) and phosphodiesterases (PDE). High intracellular levels of c-di-GMP evoke the processes leading to the production of biofilm matrix, while a decrease in its level causes an increase in cell motility and transition into the planktonic forms of growth.
Class
Cellular Processes; Cellular community - prokaryotes
Pathway map
paer02025  Biofilm formation - Pseudomonas aeruginosa
paer02025

Organism
Pseudomonas aeruginosa PA1R [GN:paer]
Gene
PA1R_gp3922  twitching motility protein PilJ [KO:K02660]
PA1R_gp3921  type IV pili signal transduction protein PilI [KO:K02659]
PA1R_gp3924  Component of chemotactic signal transduction system [KO:K06596]
PA1R_gp3926  Chemotaxis signal transduction protein [KO:K06598]
PA1R_gp3920  twitching motility protein PilH [KO:K02658]
PA1R_gp3919  twitching motility protein PilG [KO:K02657]
PA1R_gp1048  Adenylate cyclase [KO:K01768] [EC:4.6.1.1]
PA1R_gp2892  3',5'-cyclic-nucleotide phosphodiesterase [KO:K03651] [EC:3.1.4.53]
PA1R_gp0639  cAMP-binding protein - catabolite gene activator and regulatory subunit of cAMP-dependent protein kinase [KO:K10914]
PA1R_gp4152  Vfr transcriptional regulator / Cyclic AMP receptor protein [KO:K10914]
PA1R_gp3784  putative transcriptional regulator [KO:K10914]
PA1R_gp4709  Flagellar regulatory protein FleQ [KO:K10941]
PA1R_gp5292  Type III secretion thermoregulatory protein (LcrF,VirF,transcription regulation of virulence plasmid) [KO:K20968]
PA1R_gp1317  N-acyl-L-homoserine lactone synthetase RhlL [KO:K13061] [EC:2.3.1.184]
PA1R_gp1318  hypothetical protein [KO:K18099]
PA1R_gp1320  RhlA, 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs) synthase [KO:K18100] [EC:2.4.1.-]
PA1R_gp1319  RhlB, TDP-rhamnosyltransferase 1 [KO:K18101] [EC:2.4.1.-]
PA1R_gp4743  RhlC, TDP-rhamnosyltransferase 2 [KO:K12990] [EC:2.4.1.-]
PA1R_gp0366  hypothetical protein [KO:K20259]
PA1R_gp4598  Anthranilate synthase, aminase component [KO:K01657] [EC:4.1.3.27]
PA1R_gp4120  Anthranilate synthase, aminase component [KO:K01657] [EC:4.1.3.27]
PA1R_gp4599  Anthranilate synthase, amidotransferase component [KO:K01658] [EC:4.1.3.27]
PA1R_gp4149  Anthranilate synthase, amidotransferase component [KO:K01658] [EC:4.1.3.27]
PA1R_gp4593  PQS biosynthesis protein PqsA, anthranilate-CoA ligase [KO:K18000] [EC:6.2.1.32]
PA1R_gp4594  PQS biosynthesis protein PqsB, 3-oxoacyl-[acyl-carrier-protein] synthase III [KO:K18001] [EC:2.3.1.230]
PA1R_gp4595  PQS biosynthesis protein PqsC, 3-oxoacyl-[acyl-carrier-protein] synthase III [KO:K18002] [EC:2.3.1.230]
PA1R_gp4596  PQS biosynthesis protein PqsD, 3-oxoacyl-[acyl-carrier-protein] synthase III [KO:K18003] [EC:2.3.1.262]
PA1R_gp4597  PqsE, quinolone signal response protein [KO:K20257] [EC:3.1.2.32]
PA1R_gp0387  PQS biosynthesis protein PqsH, FAD-dependent monooxygenases-like protein [KO:K17940] [EC:1.14.13.182]
PA1R_gp4600  Multiple virulence factor regulator MvfR/PqsR [KO:K19735]
PA1R_gp4454  BarA sensory histidine kinase (VarS, GacS) [KO:K07678] [EC:2.7.13.3]
PA1R_gp1865  Sensor histidine kinase [KO:K20971]
PA1R_gp2777  integral membrane sensor hybrid histidine kinase [KO:K20972]
PA1R_gp0385  BarA-associated response regulator UvrY (GacA, SirA) [KO:K07689]
PA1R_gp0655  sensor histidine kinase/response regulator [KO:K20973] [EC:2.7.13.3]
PA1R_gp5192  Sensor histidine kinase/response regulator [KO:K20974] [EC:2.7.13.3]
PA1R_gp1183  Hpt domain protein [KO:K20976]
PA1R_gp1184  Serine phosphatase RsbU, regulator of sigma subunit [KO:K20977]
PA1R_gp1185  Anti-Sigma-factor antagonist [KO:K20978]
PA1R_gp1189  Negative regulator of flagellin synthesis FlgM [KO:K02398]
PA1R_gp5037  RNA polymerase sigma factor for flagellar operon [KO:K02405]
PA1R_gp3588  Serine/threonine protein kinase [KO:K11912] [EC:2.7.11.1]
PA1R_gp3589  Phosphoprotein phosphatase PppA [KO:K11915] [EC:3.1.3.16]
PA1R_gp5250  Serine/threonine protein phosphatase [KO:K11915] [EC:3.1.3.16]
PA1R_gp3590  Protein phosphatase ImpM [KO:K11890]
PA1R_gp0161  IcmF-related protein [KO:K11891]
PA1R_gp3591  IcmF-related protein [KO:K11891]
PA1R_gp5249  IcmF-related protein [KO:K11891]
PA1R_gp0163  Uncharacterized protein ImpJ/VasE [KO:K11893]
PA1R_gp3593  Uncharacterized protein ImpJ/VasE [KO:K11893]
PA1R_gp5247  Uncharacterized protein ImpJ/VasE [KO:K11893]
PA1R_gp3595  Uncharacterized protein ImpI/VasC [KO:K11913]
PA1R_gp0160  Uncharacterized protein ImpA [KO:K11902]
PA1R_gp3596  Uncharacterized protein ImpA [KO:K11902]
PA1R_gp0165  Uncharacterized protein ImpB [KO:K11901]
PA1R_gp3597  Uncharacterized protein ImpB [KO:K11901]
PA1R_gp5238  Uncharacterized protein ImpB [KO:K11901]
PA1R_gp0166  Uncharacterized protein ImpC [KO:K11900]
PA1R_gp3598  Uncharacterized protein ImpC [KO:K11900]
PA1R_gp5239  Uncharacterized protein ImpC [KO:K11900]
PA1R_gp0167  Putative cytoplasmic protein USSDB7A [KO:K11903]
PA1R_gp3599  Uncharacterized protein ImpD [KO:K11903]
PA1R_gp3202  Secreted protein Hcp [KO:K11903]
PA1R_gp5093  Secreted protein Hcp [KO:K11903]
PA1R_gp0170  Uncharacterized protein ImpH/VasB [KO:K11895]
PA1R_gp3603  Uncharacterized protein ImpH/VasB [KO:K11895]
PA1R_gp5242  Uncharacterized protein ImpH/VasB [KO:K11895]
PA1R_gp0171  ClpB protein [KO:K11907]
PA1R_gp3604  ClpB protein [KO:K11907]
PA1R_gp5243  ClpB protein [KO:K11907]
PA1R_gp1565  Methyl-accepting chemotaxis protein I (serine chemoreceptor protein) [KO:K13487]
PA1R_gp1561  Sensor histidine kinase/response regulator [KO:K13490]
PA1R_gp1564  hypothetical protein [KO:K13488]
PA1R_gp1562  CheW domain protein [KO:K13489]
PA1R_gp1560  Chemotaxis response regulator protein-glutamate methylesterase group 3 operon [KO:K13491] [EC:3.1.1.61]
PA1R_gp1559  diguanylate cyclase (GGDEF domain) with PAS/PAC sensor [KO:K11444] [EC:2.7.7.65]
PA1R_gp2231  GGDEF domain protein [KO:K21019] [EC:2.7.7.65]
PA1R_gp3683  Diguanylate cyclase (GGDEF domain) with PAS/PAC sensor [KO:K21020] [EC:2.7.7.65]
PA1R_gp4733  Inner membrane protein YfiN [KO:K21021] [EC:2.7.7.65]
PA1R_gp4719  GGDEF domain protein [KO:K21022] [EC:2.7.7.65]
PA1R_gp5305  GGDEF domain protein [KO:K21023] [EC:2.7.7.65]
PA1R_gp2267  GGDEF domain/EAL domain protein [KO:K21024] [EC:3.1.4.52]
PA1R_gp0032  capsular polysaccharide biosynthesis protein [KO:K20997]
PA1R_gp1370  Mannose-6-phosphate isomerase [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA1R_gp0033  putative phosphomannose isomerase/GDP-mannose pyrophosphorylase [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA1R_gp3387  Mannose-1-phosphate guanylyltransferase (GDP) [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA1R_gp0034  O antigen biosynthesis rhamnosyltransferase rfbN [KO:K25205]
PA1R_gp0035  polysaccharide export protein [KO:K20987]
PA1R_gp0036  exopolysaccharide biosynthesis protein [KO:K20998]
PA1R_gp0037  Extracellular Matrix protein PslF [KO:K20999]
PA1R_gp0038  Glycosyl hydrolase, family 5 [KO:K21000]
PA1R_gp0039  Glycosyl transferase, group 1 family protein [KO:K21001]
PA1R_gp0040  Extracellular Matrix protein PslI [KO:K21002]
PA1R_gp0041  membrane protein, putative [KO:K21003]
PA1R_gp0042  Virulence factor mviN [KO:K21004]
PA1R_gp0043  Extracellular Matrix protein PslL [KO:K21005]
PA1R_gp0898  Extracellular Matrix protein PelA [KO:K21006]
PA1R_gp0897  Extracellular Matrix protein PelB [KO:K21007]
PA1R_gp0896  Extracellular Matrix protein PelC [KO:K21008]
PA1R_gp0895  Extracellular Matrix protein PelD [KO:K21009]
PA1R_gp0894  Extracellular Matrix protein PelE [KO:K21010]
PA1R_gp0893  Extracellular matrix protein PelF, glycosyltransferase, group 1 [KO:K21011]
PA1R_gp0892  Extracellular Matrix protein PelG [KO:K21012]
PA1R_gp1360  Alginate biosynthesis protein Alg44 [KO:K19291] [EC:2.4.1.33]
PA1R_gp2882  PAS/PAC domain protein [KO:K21025]
PA1R_gp2881  hypothetical protein [KO:K23127]
Compound
C00044  GTP
C00575  3',5'-Cyclic AMP
C11837  N-Butyryl-L-homoserine lactone
C11848  2-Heptyl-3-hydroxy-quinolone
C16463  3',5'-Cyclic diGMP
C18076  5'-Phosphoguanylyl(3'->5')guanosine
C20643  2-Heptyl-4(1H)-quinolone
C21201  N-3-Oxo-dodecanoyl-L-homoserine lactone
Reference
  Authors
Coggan KA, Wolfgang MC
  Title
Global regulatory pathways and cross-talk control pseudomonas aeruginosa environmental lifestyle and virulence phenotype.
  Journal
Curr Issues Mol Biol 14:47-70 (2012)
Reference
  Authors
Rasamiravaka T, Labtani Q, Duez P, El Jaziri M
  Title
The formation of biofilms by Pseudomonas aeruginosa: a review of the natural and synthetic compounds interfering with control mechanisms.
  Journal
Biomed Res Int 2015:759348 (2015)
DOI:10.1155/2015/759348
Reference
  Authors
Valentini M, Filloux A
  Title
Biofilms and Cyclic di-GMP (c-di-GMP) Signaling: Lessons from Pseudomonas aeruginosa and Other Bacteria.
  Journal
J Biol Chem 291:12547-55 (2016)
DOI:10.1074/jbc.R115.711507
Reference
  Authors
Hengge R
  Title
Principles of c-di-GMP signalling in bacteria.
  Journal
Nat Rev Microbiol 7:263-73 (2009)
DOI:10.1038/nrmicro2109
Reference
  Authors
Liang ZX
  Title
The expanding roles of c-di-GMP in the biosynthesis of exopolysaccharides and secondary metabolites.
  Journal
Nat Prod Rep 32:663-83 (2015)
DOI:10.1039/c4np00086b
Reference
  Authors
Fulcher NB, Holliday PM, Klem E, Cann MJ, Wolfgang MC
  Title
The Pseudomonas aeruginosa Chp chemosensory system regulates intracellular cAMP levels by modulating adenylate cyclase activity.
  Journal
Mol Microbiol 76:889-904 (2010)
DOI:10.1111/j.1365-2958.2010.07135.x
Reference
  Authors
Marsden AE, Intile PJ, Schulmeyer KH, Simmons-Patterson ER, Urbanowski ML, Wolfgang MC, Yahr TL
  Title
Vfr Directly Activates exsA Transcription To Regulate Expression of the Pseudomonas aeruginosa Type III Secretion System.
  Journal
J Bacteriol 198:1442-50 (2016)
DOI:10.1128/JB.00049-16
Reference
  Authors
Brencic A, Lory S
  Title
Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA.
  Journal
Mol Microbiol 72:612-32 (2009)
DOI:10.1111/j.1365-2958.2009.06670.x
Reference
  Authors
Hsu JL, Chen HC, Peng HL, Chang HY
  Title
Characterization of the histidine-containing phosphotransfer protein B-mediated multistep phosphorelay system in Pseudomonas aeruginosa PAO1.
  Journal
J Biol Chem 283:9933-44 (2008)
DOI:10.1074/jbc.M708836200
Reference
  Authors
Guvener ZT, Harwood CS
  Title
Subcellular location characteristics of the Pseudomonas aeruginosa GGDEF protein, WspR, indicate that it produces cyclic-di-GMP in response to growth on surfaces.
  Journal
Mol Microbiol 66:1459-73 (2007)
DOI:10.1111/j.1365-2958.2007.06008.x
Reference
  Authors
Irie Y, Starkey M, Edwards AN, Wozniak DJ, Romeo T, Parsek MR
  Title
Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA.
  Journal
Mol Microbiol 78:158-72 (2010)
DOI:10.1111/j.1365-2958.2010.07320.x
Related
pathway
paer02024  Quorum sensing
paer02040  Flagellar assembly
paer03070  Bacterial secretion system
KO pathway
ko02025   
LinkDB

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