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 K02660 twitching motility protein PilJ K02659 twitching motility protein PilI K06596 chemosensory pili system protein ChpA (sensor histidine kinase/response regulator) K06598 chemosensory pili system protein ChpC K02658 twitching motility two-component system response regulator PilH K02657 twitching motility two-component system response regulator PilG K01768 adenylate cyclase [EC:4.6.1.1] K03651 3',5'-cyclic-AMP phosphodiesterase [EC:3.1.4.53] K10914 CRP/FNR family transcriptional regulator, cyclic AMP receptor protein K10941 sigma-54 dependent transcriptional regulator, flagellar regulatory protein K20968 AraC family transcriptional regulator, exoenzyme S synthesis regulatory protein ExsA K13060 acyl homoserine lactone synthase [EC:2.3.1.184] K18304 LuxR family transcriptional regulator, quorum-sensing system regulator LasR K13061 acyl homoserine lactone synthase [EC:2.3.1.184] K18099 LuxR family transcriptional regulator, quorum-sensing system regulator RhlR K18100 rhamnosyltransferase subunit A [EC:2.4.1.-] K18101 rhamnosyltransferase subunit B [EC:2.4.1.-] K12990 rhamnosyltransferase [EC:2.4.1.-] K20258 PA-I galactophilic lectin K20259 PA-IIL fucose-binding lectin K01657 anthranilate synthase component I [EC:4.1.3.27] K01658 anthranilate synthase component II [EC:4.1.3.27] K18000 anthranilate-CoA ligase [EC:6.2.1.32] K18001 2-heptyl-4(1H)-quinolone synthase subunit PqsB [EC:2.3.1.230] K18002 2-heptyl-4(1H)-quinolone synthase subunit PqsC [EC:2.3.1.230] K18003 anthraniloyl-CoA anthraniloyltransferase [EC:2.3.1.262] K20257 2-aminobenzoylacetyl-CoA thioesterase [EC:3.1.2.32] K17940 2-heptyl-3-hydroxy-4(1H)-quinolone synthase [EC:1.14.13.182] K19735 LysR family transcriptional regulator, quorum-sensing system regulator MvfR K07678 two-component system, NarL family, sensor histidine kinase BarA [EC:2.7.13.3] K20971 two-component system, sensor histidine kinase LadS K20972 two-component system, sensor histidine kinase RetS K07689 two-component system, NarL family, invasion response regulator UvrY K20969 small regulatory RNA RsmY K20970 small regulatory RNA RsmZ K03563 carbon storage regulator K20973 two-component system, sensor histidine kinase SagS [EC:2.7.13.3] K20974 two-component system, sensor histidine kinase [EC:2.7.13.3] K20975 two-component system, sensor histidine kinase [EC:2.7.13.3] K20976 histidine phosphotransfer protein HptB K20977 two-component system, HptB-dependent secretion and biofilm response regulator K20978 HptB-dependent secretion and biofilm anti anti-sigma factor K02398 negative regulator of flagellin synthesis FlgM K02405 RNA polymerase sigma factor FliA K11912 serine/threonine-protein kinase PpkA [EC:2.7.11.1] K11915 serine/threonine protein phosphatase Stp1 [EC:3.1.3.16] K11890 type VI secretion system protein ImpM K11891 type VI secretion system protein ImpL K11893 type VI secretion system protein ImpJ K11913 type VI secretion system protein K11902 type VI secretion system protein ImpA K11901 type VI secretion system protein ImpB K11900 type VI secretion system protein ImpC K11903 type VI secretion system secreted protein Hcp K11895 type VI secretion system protein ImpH K11907 type VI secretion system protein VasG K13487 methyl-accepting chemotaxis protein WspA K13490 two-component system, chemotaxis family, sensor histidine kinase and response regulator WspE K13488 chemotaxis-related protein WspB K13489 chemotaxis-related protein WspD K13491 two-component system, chemotaxis family, response regulator WspF [EC:3.1.1.61] K11444 two-component system, chemotaxis family, response regulator WspR [EC:2.7.7.65] K21019 diguanylate cyclase [EC:2.7.7.65] K21020 diguanylate cyclase [EC:2.7.7.65] K21021 diguanylate cyclase [EC:2.7.7.65] K21022 diguanylate cyclase [EC:2.7.7.65] K21023 diguanylate cyclase [EC:2.7.7.65] K21024 c-di-GMP phosphodiesterase [EC:3.1.4.52] K20997 polysaccharide biosynthesis protein PslA K16011 mannose-1-phosphate guanylyltransferase / mannose-6-phosphate isomerase [EC:2.7.7.13 5.3.1.8] K25205 polysaccharide biosynthesis protein PslC K20987 polysaccharide biosynthesis/export protein PslD K20998 polysaccharide biosynthesis protein PslE K20999 polysaccharide biosynthesis protein PslF K21000 polysaccharide biosynthesis protein PslG K21001 polysaccharide biosynthesis protein PslH K21002 polysaccharide biosynthesis protein PslI K21003 polysaccharide biosynthesis protein PslJ K21004 polysaccharide biosynthesis protein PslK K21005 polysaccharide biosynthesis protein PslL K21006 polysaccharide biosynthesis protein PelA K21007 polysaccharide biosynthesis protein PelB K21008 polysaccharide biosynthesis protein PelC K21009 polysaccharide biosynthesis protein PelD K21010 polysaccharide biosynthesis protein PelE K21011 polysaccharide biosynthesis protein PelF K21012 polysaccharide biosynthesis protein PelG K19291 mannuronan synthase [EC:2.4.1.33] K21025 multidomain signaling protein FimX K23127 cyclic-di-GMP-binding protein 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 ///