KEGG   PATHWAY: pae02025
Entry
pae02025                    Pathway                                
Name
Biofilm formation - Pseudomonas aeruginosa - Pseudomonas aeruginosa PAO1
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
pae02025  Biofilm formation - Pseudomonas aeruginosa
pae02025

Organism
Pseudomonas aeruginosa PAO1 [GN:pae]
Gene
PA0411  pilJ; twitching motility protein PilJ [KO:K02660]
PA0410  pilI; twitching motility protein PilI [KO:K02659]
PA0413  chpA; chemotactic signal transduction system protein [KO:K06596]
PA0415  chpC; chemotaxis protein [KO:K06598]
PA0409  pilH; twitching motility protein PilH [KO:K02658]
PA0408  pilG; pilus biosynthesis/twitching motility protein PilG [KO:K02657]
PA3217  cyaB; protein CyaB [KO:K01768] [EC:4.6.1.1]
PA4969  cpdA; cAMP phosphodiesterase [KO:K03651] [EC:3.1.4.53]
PA0652  vfr; cAMP-regulatory protein [KO:K10914]
PA0275  transcriptional regulator [KO:K10914]
PA1097  fleQ; transcriptional regulator FleQ [KO:K10941]
PA1713  exsA; exoenzyme S transcriptional regulator ExsA [KO:K20968]
PA1432  lasI; acyl-homoserine-lactone synthase [KO:K13060] [EC:2.3.1.184]
PA1430  lasR; transcriptional regulator LasR [KO:K18304]
PA3476  rhlI; acyl-homoserine-lactone synthase [KO:K13061] [EC:2.3.1.184]
PA3477  rhlR; transcriptional regulator RhlR [KO:K18099]
PA3479  rhlA; rhamnosyltransferase subunit A [KO:K18100] [EC:2.4.1.-]
PA3478  rhlB; rhamnosyltransferase subunit B [KO:K18101] [EC:2.4.1.-]
PA1130  rhlC; rhamnosyltransferase [KO:K12990] [EC:2.4.1.-]
PA2570  lecA; PA-I galactophilic lectin [KO:K20258]
PA2569  hypothetical protein [KO:K20259]
PA0609  trpE; anthranilate synthase component I [KO:K01657] [EC:4.1.3.27]
PA1001  phnA; anthranilate synthase component I [KO:K01657] [EC:4.1.3.27]
PA0649  trpG; anthranilate synthase component II [KO:K01658] [EC:4.1.3.27]
PA1002  phnB; anthranilate synthase component II [KO:K01658] [EC:4.1.3.27]
PA0996  pqsA; anthranilate--CoA ligase [KO:K18000] [EC:6.2.1.32]
PA0997  pqsB; hypothetical protein [KO:K18001] [EC:2.3.1.230]
PA0998  pqsC; hypothetical protein [KO:K18002] [EC:2.3.1.230]
PA0999  pqsD; 3-oxoacyl-ACP synthase [KO:K18003] [EC:2.3.1.262]
PA1000  pqsE; thioesterase PqsE [KO:K20257] [EC:3.1.2.32]
PA2587  pqsH; 2-heptyl-3-hydroxy-4(1H)-quinolone synthase [KO:K17940] [EC:1.14.13.182]
PA1003  mvfR; transcriptional regulator MvfR [KO:K19735]
PA0928  gacS; sensor/response regulator hybrid protein [KO:K07678] [EC:2.7.13.3]
PA3974  ladS; lost adherence sensor LadS [KO:K20971]
PA4856  retS; sensor histidine kinase MifS [KO:K20972]
PA2586  gacA; response regulator GacA [KO:K07689]
PA0527.1  rsmY; regulatory RNA RsmY [KO:K20969]
PA3621.1  rsmZ; regulatory RNA RsmZ [KO:K20970]
PA0905  rsmA; carbon storage regulator [KO:K03563]
PA2824  sensor/response regulator hybrid protein [KO:K20973] [EC:2.7.13.3]
PA1611  sensor/response regulator hybrid protein [KO:K20974] [EC:2.7.13.3]
PA1976  ercS'; sensor histidine kinase [KO:K20975] [EC:2.7.13.3]
PA3345  hypothetical protein [KO:K20976]
PA3346  two-component response regulator [KO:K20977]
PA3347  hypothetical protein [KO:K20978]
PA3351  flgM; protein FlgM [KO:K02398]
PA1455  fliA; flagellar biosynthesis sigma factor FliA [KO:K02405]
PA0074  ppkA; serine/threonine protein kinase PpkA [KO:K11912] [EC:2.7.11.1]
PA1670  stp1; serine/threonine phosphoprotein phosphatase Stp1 [KO:K11915] [EC:3.1.3.16]
PA0075  pppA; serine/threonine phosphatase [KO:K11915] [EC:3.1.3.16]
PA0076  hypothetical protein [KO:K11890]
PA1669  hypothetical protein [KO:K11891]
PA2361  hypothetical protein [KO:K11891]
PA0077  icmF1; type VI secretion protein IcmF [KO:K11891]
PA1667  hypothetical protein [KO:K11893]
PA2363  hypothetical protein [KO:K11893]
PA0079  hypothetical protein [KO:K11893]
PA0081  fha1; Fha domain-containing protein [KO:K11913]
PA0082  hypothetical protein [KO:K11902]
PA2360  hypothetical protein [KO:K11902]
PA1657  hypothetical protein [KO:K11901]
PA0083  hypothetical protein [KO:K11901]
PA2365  hypothetical protein [KO:K11901]
PA0084  hypothetical protein [KO:K11900]
PA2366  uricase [KO:K11900]
PA1658  hypothetical protein [KO:K11900]
PA1512  hcpA; secreted protein Hcp [KO:K11903]
PA2367  hypothetical protein [KO:K11903]
PA0263  hcpC; secreted protein Hcp [KO:K11903]
PA5267  hcpB; secreted protein Hcp [KO:K11903]
PA0085  hcp1; protein secretion apparatus assembly protein [KO:K11903]
PA2370  hypothetical protein [KO:K11895]
PA1661  hypothetical protein [KO:K11895]
PA0089  hypothetical protein [KO:K11895]
PA1662  ClpA/B-type protease [KO:K11907]
PA0090  clpV1; secretion protein ClpV1 [KO:K11907]
PA2371  ClpA/B-type protease [KO:K11907]
PA3708  wspA; chemotaxis transducer [KO:K13487]
PA3704  wspE; chemotaxis sensor/effector fusion protein [KO:K13490]
PA3707  hypothetical protein [KO:K13488]
PA3705  wspD; hypothetical protein [KO:K13489]
PA3703  wspF; chemotaxis-specific methylesterase [KO:K13491] [EC:3.1.1.61]
PA3702  wspR; two-component response regulator [KO:K11444] [EC:2.7.7.65]
PA4332  hypothetical protein [KO:K21019] [EC:2.7.7.65]
PA0169  hypothetical protein [KO:K21020] [EC:2.7.7.65]
PA1120  tpbB; diguanylate cyclase [KO:K21021] [EC:2.7.7.65]
PA1107  hypothetical protein [KO:K21022] [EC:2.7.7.65]
PA1727  mucR; signaling protein [KO:K21023] [EC:2.7.7.65]
PA4367  bifA; protein BifA [KO:K21024] [EC:3.1.4.52]
PA2231  pslA; biofilm formation protein PslA [KO:K20997]
PA3551  algA; bifunctional mannose-1-phosphate guanylyltransferase/mannose-6-phosphate isomerase [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA2232  pslB; biofilm formation protein PslB [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA5452  wbpW; phosphomannose isomerase/mannose-1-phosphate guanylyl transferase [KO:K16011] [EC:2.7.7.13 5.3.1.8]
PA2233  pslC; biofilm formation protein PslC [KO:K25205]
PA2234  pslD; biofilm formation protein PslD [KO:K20987]
PA2235  pslE; biofilm formation protein PslE [KO:K20998]
PA2236  pslF; biofilm formation protein PslF [KO:K20999]
PA2237  pslG; biofilm formation protein PslG [KO:K21000]
PA2238  pslH; biofilm formation protein PslH [KO:K21001]
PA2239  pslI; biofilm formation protein PslI [KO:K21002]
PA2240  pslJ; biofilm formation protein PslJ [KO:K21003]
PA2241  pslK; biofilm formation protein PslL [KO:K21004]
PA2242  pslL; hypothetical protein [KO:K21005]
PA3064  pelA; hypothetical protein [KO:K21006]
PA3063  pelB; pellicle/biofilm biosynthesis protein PelB [KO:K21007]
PA3062  pelC; pellicle/biofilm biosynthesis outer membrane protein PelC [KO:K21008]
PA3061  pelD; pellicle/biofilm biosynthesis protein PelD [KO:K21009]
PA3060  pelE; pellicle/biofilm biosynthesis protein PelE [KO:K21010]
PA3059  pelF; pellicle/biofilm biosynthesis glycosyltransferase PelF [KO:K21011]
PA3058  pelG; pellicle/biofilm biosynthesis Wzx-like polysaccharide transporter PelG [KO:K21012]
PA3542  alg44; alginate biosynthesis protein Alg44 [KO:K19291] [EC:2.4.1.33]
PA4959  fimX; protein FimX [KO:K21025]
PA4958  fimW; cyclic-di-GMP receptor FimW [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
pae02024  Quorum sensing
pae02040  Flagellar assembly
pae03070  Bacterial secretion system
KO pathway
ko02025   
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