ENTRY ko02025 Pathway NAME Biofilm formation - Pseudomonas aeruginosa 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 ko02025 Biofilm formation - Pseudomonas aeruginosa ORTHOLOGY K01657 trpE; anthranilate synthase component I [EC:4.1.3.27] K01658 trpG; anthranilate synthase component II [EC:4.1.3.27] K01768 E4.6.1.1; adenylate cyclase [EC:4.6.1.1] K02398 flgM; negative regulator of flagellin synthesis FlgM K02405 fliA, whiG; RNA polymerase sigma factor FliA K02657 pilG; twitching motility two-component system response regulator PilG K02658 pilH; twitching motility two-component system response regulator PilH K02659 pilI; twitching motility protein PilI K02660 pilJ; twitching motility protein PilJ K03563 csrA; carbon storage regulator K03651 cpdA; 3',5'-cyclic-AMP phosphodiesterase [EC:3.1.4.53] K06596 chpA; chemosensory pili system protein ChpA (sensor histidine kinase/response regulator) K06598 chpC; chemosensory pili system protein ChpC K07678 barA, gacS, varS; two-component system, NarL family, sensor histidine kinase BarA [EC:2.7.13.3] K07689 uvrY, gacA, varA; two-component system, NarL family, invasion response regulator UvrY K10914 crp; CRP/FNR family transcriptional regulator, cyclic AMP receptor protein K10941 flrA, fleQ, flaK; sigma-54 dependent transcriptional regulator, flagellar regulatory protein K11444 wspR; two-component system, chemotaxis family, response regulator WspR [EC:2.7.7.65] K11890 impM; type VI secretion system protein ImpM K11891 impL, vasK, icmF; type VI secretion system protein ImpL K11893 impJ, vasE; type VI secretion system protein ImpJ K11895 impH, vasB; type VI secretion system protein ImpH K11900 impC; type VI secretion system protein ImpC K11901 impB; type VI secretion system protein ImpB K11902 impA; type VI secretion system protein ImpA K11903 hcp; type VI secretion system secreted protein Hcp K11907 vasG, clpV; type VI secretion system protein VasG K11912 ppkA; serine/threonine-protein kinase PpkA [EC:2.7.11.1] K11913 fha1; type VI secretion system protein K11915 stp1, pppA; serine/threonine protein phosphatase Stp1 [EC:3.1.3.16] K12990 rfbF, rhlC; rhamnosyltransferase [EC:2.4.1.-] K13060 lasI; acyl homoserine lactone synthase [EC:2.3.1.184] K13061 rhlI, phzI, solI, cepI, tofI; acyl homoserine lactone synthase [EC:2.3.1.184] K13487 wspA; methyl-accepting chemotaxis protein WspA K13488 wspB; chemotaxis-related protein WspB K13489 wspD; chemotaxis-related protein WspD K13490 wspE; two-component system, chemotaxis family, sensor histidine kinase and response regulator WspE K13491 wspF; two-component system, chemotaxis family, response regulator WspF [EC:3.1.1.61] K16011 algA, xanB, rfbA, wbpW, pslB; mannose-1-phosphate guanylyltransferase / mannose-6-phosphate isomerase [EC:2.7.7.13 5.3.1.8] K17940 pqsH; 2-heptyl-3-hydroxy-4(1H)-quinolone synthase [EC:1.14.13.182] K18000 pqsA; anthranilate-CoA ligase [EC:6.2.1.32] K18001 pqsB; 2-heptyl-4(1H)-quinolone synthase subunit PqsB [EC:2.3.1.230] K18002 pqsC; 2-heptyl-4(1H)-quinolone synthase subunit PqsC [EC:2.3.1.230] K18003 pqsD; anthraniloyl-CoA anthraniloyltransferase [EC:2.3.1.262] K18099 rhlR, phzR; LuxR family transcriptional regulator, quorum-sensing system regulator RhlR K18100 rhlA; rhamnosyltransferase subunit A [EC:2.4.1.-] K18101 rhlB; rhamnosyltransferase subunit B [EC:2.4.1.-] K18304 lasR; LuxR family transcriptional regulator, quorum-sensing system regulator LasR K19291 alg44; mannuronan synthase [EC:2.4.1.33] K19735 mvfR, pqsR; LysR family transcriptional regulator, quorum-sensing system regulator MvfR K20257 pqsE; 2-aminobenzoylacetyl-CoA thioesterase [EC:3.1.2.32] K20258 lecA; PA-I galactophilic lectin K20259 lecB; PA-IIL fucose-binding lectin K20968 exsA; AraC family transcriptional regulator, exoenzyme S synthesis regulatory protein ExsA K20969 rsmY; small regulatory RNA RsmY K20970 rsmZ; small regulatory RNA RsmZ K20971 ladS; two-component system, sensor histidine kinase LadS K20972 retS; two-component system, sensor histidine kinase RetS K20973 sagS; two-component system, sensor histidine kinase SagS [EC:2.7.13.3] K20974 K20974; two-component system, sensor histidine kinase [EC:2.7.13.3] K20975 K20975; two-component system, sensor histidine kinase [EC:2.7.13.3] K20976 hptB; histidine phosphotransfer protein HptB K20977 hsbR; two-component system, HptB-dependent secretion and biofilm response regulator K20978 hsbA; HptB-dependent secretion and biofilm anti anti-sigma factor K20987 pslD; polysaccharide biosynthesis/export protein PslD K20997 pslA; polysaccharide biosynthesis protein PslA K20998 pslE; polysaccharide biosynthesis protein PslE K20999 pslF; polysaccharide biosynthesis protein PslF K21000 pslG; polysaccharide biosynthesis protein PslG K21001 pslH; polysaccharide biosynthesis protein PslH K21002 pslI; polysaccharide biosynthesis protein PslI K21003 pslJ; polysaccharide biosynthesis protein PslJ K21004 pslK; polysaccharide biosynthesis protein PslK K21005 pslL; polysaccharide biosynthesis protein PslL K21006 pelA; polysaccharide biosynthesis protein PelA K21007 pelB; polysaccharide biosynthesis protein PelB K21008 pelC; polysaccharide biosynthesis protein PelC K21009 pelD; polysaccharide biosynthesis protein PelD K21010 pelE; polysaccharide biosynthesis protein PelE K21011 pelF; polysaccharide biosynthesis protein PelF K21012 pelG; polysaccharide biosynthesis protein PelG K21019 sadC; diguanylate cyclase [EC:2.7.7.65] K21020 siaD; diguanylate cyclase [EC:2.7.7.65] K21021 tpbB; diguanylate cyclase [EC:2.7.7.65] K21022 roeA; diguanylate cyclase [EC:2.7.7.65] K21023 mucR; diguanylate cyclase [EC:2.7.7.65] K21024 bifA; c-di-GMP phosphodiesterase [EC:3.1.4.52] K21025 fimX; multidomain signaling protein FimX K23127 fimW; cyclic-di-GMP-binding protein K25205 pslC; polysaccharide biosynthesis protein PslC 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 PMID:22354680 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 PMID:25866808 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 PMID:27129226 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 PMID:19287449 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 PMID:25666534 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 PMID:20345659 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 PMID:26929300 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 PMID:19426209 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 PMID:18256026 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 PMID:18028314 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 PMID:20735777 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 REL_PATHWAY ko02024 Quorum sensing ko02040 Flagellar assembly ko03070 Bacterial secretion system ///