ENTRY ko05111 Pathway NAME Biofilm formation - Vibrio cholerae DESCRIPTION Surface colonization and subsequent biofilm formation and development provide numerous advantages to microorganisms. On the other hand, biofilm formation is an energetically costly process and therefore must be tightly regulated and plastic, enabling biofilm bacteria to be responsive to the various environmental cues. The quorum sensing (QS) pathway of Vibrio cholerae activates the expression of VpsR, VpsT and AphA (the main activators of biofilm formation) at low cell density and HapR (the main repressor) at high cell density. At low cell density, biofilm genes, including Vibrio polysaccharide (VPS) biosynthesis genes and the major extracellular matrix genes RbmA, RbmC, and Bap1, are expressed. The QS pathway also leads to induction of virulence factors such as toxin coregulated pilus (TCP) and cholera toxin (CTX), essential for colonization of the host and enterotoxicity, respectively. The VarS/VarA signaling system responds to an unknown environmental cue and represses biofilm production by process which involves the regulatory sRNAs CsrB, CsrC and CsrD and the RNA-binding protein CsrA, interfering with LuxO of the QS pathway. The second messenger cAMP acts as a repressor of biofilm formation. cAMP is generated by adenylate cyclase CyaA, and in complex with cAMP receptor protein (CRP), this nucleotide has been shown to upregulate HapR production through the positive regulation of the CAI-I synthase CqsA and the negative regulation of Fis. The second messenger c-di-GMP is a key signalling molecule controlling motility and biofilm matrix production. High cellular levels of c-di-GMP promote enhanced transcription of genes involved in biofilm formation, possibly by promoting VpsT-mediated transcriptional activation of vps genes. CLASS Cellular Processes; Cellular community - prokaryotes PATHWAY_MAP ko05111 Biofilm formation - Vibrio cholerae MODULE M00852 Vibrio cholerae pathogenicity signature, toxin coregulated pilus [PATH:ko05111] ORTHOLOGY K00640 cysE; serine O-acetyltransferase [EC:2.3.1.30] K01791 wecB; UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) [EC:5.1.3.14] K01912 paaK; phenylacetate-CoA ligase [EC:6.2.1.30] K02405 fliA, whiG; RNA polymerase sigma factor FliA K02452 gspC; general secretion pathway protein C K02453 gspD; general secretion pathway protein D K02454 gspE; general secretion pathway protein E [EC:7.4.2.8] K02455 gspF; general secretion pathway protein F K02456 gspG; general secretion pathway protein G K02457 gspH; general secretion pathway protein H K02458 gspI; general secretion pathway protein I K02459 gspJ; general secretion pathway protein J K02460 gspK; general secretion pathway protein K K02461 gspL; general secretion pathway protein L K02462 gspM; general secretion pathway protein M K02463 gspN; general secretion pathway protein N K02472 wecC; UDP-N-acetyl-D-mannosaminuronic acid dehydrogenase [EC:1.1.1.336] K02777 crr; sugar PTS system EIIA component [EC:2.7.1.-] K02779 ptsG; glucose PTS system EIICB or EIICBA component [EC:2.7.1.199] K03087 rpoS; RNA polymerase nonessential primary-like sigma factor K03092 rpoN; RNA polymerase sigma-54 factor K03557 fis; Fis family transcriptional regulator, factor for inversion stimulation protein K03563 csrA; carbon storage regulator K03606 wcaJ; undecaprenyl-phosphate glucose phosphotransferase [EC:2.7.8.31] K03666 hfq; host factor-I protein K05851 cyaA; adenylate cyclase, class 1 [EC:4.6.1.1] K07173 luxS; S-ribosylhomocysteine lyase [EC:4.4.1.21] K07181 cdgJ; c-di-GMP phosphodiesterase [EC:3.1.4.52] 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 K08604 hap, nprV; vibriolysin [EC:3.4.24.25] K08720 ompU; outer membrane protein OmpU K10909 luxQ; two-component system, autoinducer 2 sensor kinase/phosphatase LuxQ [EC:2.7.13.3 3.1.3.-] K10910 luxP; autoinducer 2-binding periplasmic protein LuxP K10911 luxU; two-component system, phosphorelay protein LuxU K10912 luxO; two-component system, repressor protein LuxO K10913 hapR, luxR, litR; TetR/AcrR family transcriptional regulator, hemagglutinin/protease regulatory protein K10914 crp; CRP/FNR family transcriptional regulator, cyclic AMP receptor protein K10915 cqsA; CAI-1 autoinducer synthase [EC:2.3.-.-] K10916 cqsS; two-component system, CAI-1 autoinducer sensor kinase/phosphatase CqsS [EC:2.7.13.3 3.1.3.-] K10917 aphA; PadR family transcriptional regulator, regulatory protein AphA K10918 aphB; LysR family transcriptional regulator, transcriptional activator AphB K10919 tcpH; toxin coregulated pilus biosynthesis protein H K10920 tcpP; toxin coregulated pilus biosynthesis protein P K10921 toxR; cholera toxin transcriptional activator K10922 toxS; transmembrane regulatory protein ToxS K10923 tcpN, toxT; AraC family transcriptional regulator, TCP pilus virulence regulatory protein K10924 mshA; MSHA pilin protein MshA K10925 mshB; MSHA pilin protein MshB K10926 mshC; MSHA pilin protein MshC K10927 mshD; MSHA pilin protein MshD K10928 ctxA; cholera enterotoxin subunit A [EC:2.4.2.36] K10929 ctxB; cholera enterotoxin subunit B K10930 tcpA; toxin coregulated pilin K10931 tcpB; toxin coregulated pilus biosynthesis protein B K10932 tcpC; toxin coregulated pilus biosynthesis outer membrane protein C K10933 tcpD; toxin coregulated pilus biosynthesis protein D K10934 tcpE; toxin coregulated pilus biosynthesis protein E K10935 tcpF; toxin coregulated pilus biosynthesis protein F K10936 acfA; accessory colonization factor AcfA K10937 acfB; accessory colonization factor AcfB K10938 acfC; accessory colonization factor AcfC K10939 acfD; accessory colonization factor AcfD K10940 ompT; outer membrane protein OmpT K10941 flrA, fleQ, flaK; sigma-54 dependent transcriptional regulator, flagellar regulatory protein K10942 flrB, fleS, flaL; two-component system, sensor histidine kinase FlrB [EC:2.7.13.3] K10943 flrC, fleR, flaM; two-component system, response regulator FlrC K10961 tcpI; toxin coregulated pilus biosynthesis protein I K10962 tcpQ; toxin coregulated pilus biosynthesis protein Q K10963 tcpR; toxin coregulated pilus biosynthesis protein R K10964 tcpS; toxin coregulated pilus biosynthesis protein S K10965 tcpT; toxin coregulated pilus biosynthesis protein T K12276 mshE; MSHA biogenesis protein MshE K13246 vieA; c-di-GMP phosphodiesterase [EC:3.1.4.52] K15851 qrr; quorum regulatory RNA Qrr K16554 exoP, vpsO; polysaccharide biosynthesis transport protein [EC:2.7.10.3] K18515 csrB; small regulatory RNA CsrB K20918 vpsT; LuxR family transcriptional regulator, positive regulator of biofilm formation K20919 vpsR, cpsR; sigma-54 dependent transcriptional regulator, positive regulator of biofilm formation K20920 vpsM; polysaccharide biosynthesis protein VpsM K20921 vpsD, epsF; polysaccharide biosynthesis protein VpsD K20922 vpsI; polysaccharide biosynthesis protein VpsI K20945 vpsU; tyrosine-protein phosphatase [EC:3.1.3.48] K20946 vpsE; polysaccharide biosynthesis protein VpsE K20947 vpsF; polysaccharide biosynthesis protein VpsF K20948 vpsJ; polysaccharide biosynthesis protein VpsJ K20949 vpsP; polysaccharide biosynthesis protein VpsP K20950 vpsQ; polysaccharide biosynthesis protein VpsQ K20951 bap1; extracellular matrix protein K20952 rbmC; rugosity and biofilm structure modulator C K20953 rbmA; rugosity and biofilm structure modulator A K20954 acgB; diguanylate cyclase [EC:2.7.7.65] K20955 cdgK; diguanylate cyclase [EC:2.7.7.65] K20956 cdgA; diguanylate cyclase [EC:2.7.7.65] K20957 cdgH; diguanylate cyclase [EC:2.7.7.65] K20958 cdgL; diguanylate cyclase [EC:2.7.7.65] K20959 cdgM; diguanylate cyclase [EC:2.7.7.65] K20960 K20960; diguanylate cyclase [EC:2.7.7.65] K20961 vpvC; diguanylate cyclase [EC:2.7.7.65] K20962 cdgC; c-di-GMP phosphodiesterase [EC:3.1.4.52] K20963 acgA; c-di-GMP phosphodiesterase [EC:3.1.4.52] K20964 cdpA; c-di-GMP phosphodiesterase [EC:3.1.4.52] K20965 rocS; c-di-GMP phosphodiesterase [EC:3.1.4.52] K20966 mbaA; c-di-GMP phosphodiesterase [EC:3.1.4.52] K20988 vpsN; polysaccharide biosynthesis/export protein VpsN K25886 vpsK; polysaccharide biosynthesis protein VpsK COMPOUND C00031 D-Glucose C00044 GTP C00092 D-Glucose 6-phosphate C00575 3',5'-Cyclic AMP C16421 AI-2 C16463 3',5'-Cyclic diGMP C16640 CAI-1 C18076 5'-Phosphoguanylyl(3'->5')guanosine REFERENCE PMID:25895940 AUTHORS Teschler JK, Zamorano-Sanchez D, Utada AS, Warner CJ, Wong GC, Linington RG, Yildiz FH TITLE Living in the matrix: assembly and control of Vibrio cholerae biofilms. JOURNAL Nat Rev Microbiol 13:255-68 (2015) DOI:10.1038/nrmicro3433 REFERENCE PMID:26700108 AUTHORS Dang H, Lovell CR TITLE Microbial Surface Colonization and Biofilm Development in Marine Environments. JOURNAL Microbiol Mol Biol Rev 80:91-138 (2016) DOI:10.1128/MMBR.00037-15 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:9371445 AUTHORS Sandkvist M, Michel LO, Hough LP, Morales VM, Bagdasarian M, Koomey M, DiRita VJ, Bagdasarian M TITLE General secretion pathway (eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae. JOURNAL J Bacteriol 179:6994-7003 (1997) DOI:10.1128/JB.179.22.6994-7003.1997 REFERENCE PMID:16262799 AUTHORS Lenz DH, Miller MB, Zhu J, Kulkarni RV, Bassler BL TITLE CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae. JOURNAL Mol Microbiol 58:1186-202 (2005) DOI:10.1111/j.1365-2958.2005.04902.x REFERENCE PMID:17981973 AUTHORS Houot L, Watnick PI TITLE A novel role for enzyme I of the Vibrio cholerae phosphoenolpyruvate phosphotransferase system in regulation of growth in a biofilm. JOURNAL J Bacteriol 190:311-20 (2008) DOI:10.1128/JB.01410-07 REFERENCE PMID:17921282 AUTHORS Liang W, Silva AJ, Benitez JA TITLE The cyclic AMP receptor protein modulates colonial morphology in Vibrio cholerae. JOURNAL Appl Environ Microbiol 73:7482-7 (2007) DOI:10.1128/AEM.01564-07 REFERENCE PMID:17181781 AUTHORS Lenz DH, Bassler BL TITLE The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing. JOURNAL Mol Microbiol 63:859-71 (2007) DOI:10.1111/j.1365-2958.2006.05545.x REL_PATHWAY ko02024 Quorum sensing ko02040 Flagellar assembly ko03070 Bacterial secretion system ko05110 Vibrio cholerae infection ///