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 K07173 S-ribosylhomocysteine lyase [EC:4.4.1.21] K10909 two-component system, autoinducer 2 sensor kinase/phosphatase LuxQ [EC:2.7.13.3 3.1.3.-] K10910 autoinducer 2-binding periplasmic protein LuxP K10915 CAI-1 autoinducer synthase [EC:2.3.-.-] K10916 two-component system, CAI-1 autoinducer sensor kinase/phosphatase CqsS [EC:2.7.13.3 3.1.3.-] K10911 two-component system, phosphorelay protein LuxU K10912 two-component system, repressor protein LuxO K15851 quorum regulatory RNA Qrr K03666 host factor-I protein K10917 PadR family transcriptional regulator, regulatory protein AphA K10918 LysR family transcriptional regulator, transcriptional activator AphB K20918 LuxR family transcriptional regulator, positive regulator of biofilm formation K20919 sigma-54 dependent transcriptional regulator, positive regulator of biofilm formation K20945 tyrosine-protein phosphatase [EC:3.1.3.48] K01791 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) [EC:5.1.3.14] K02472 UDP-N-acetyl-D-mannosaminuronic acid dehydrogenase [EC:1.1.1.336] K00640 serine O-acetyltransferase [EC:2.3.1.30] K20921 polysaccharide biosynthesis protein VpsD K20946 polysaccharide biosynthesis protein VpsE K20947 polysaccharide biosynthesis protein VpsF K01912 phenylacetate-CoA ligase [EC:6.2.1.30] K20922 polysaccharide biosynthesis protein VpsI K20948 polysaccharide biosynthesis protein VpsJ K25886 polysaccharide biosynthesis protein VpsK K03606 undecaprenyl-phosphate glucose phosphotransferase [EC:2.7.8.31] K20920 polysaccharide biosynthesis protein VpsM K20988 polysaccharide biosynthesis/export protein VpsN K16554 polysaccharide biosynthesis transport protein [EC:2.7.10.3] K20949 polysaccharide biosynthesis protein VpsP K20950 polysaccharide biosynthesis protein VpsQ K02452 general secretion pathway protein C K02453 general secretion pathway protein D K02454 general secretion pathway protein E [EC:7.4.2.8] K02455 general secretion pathway protein F K02456 general secretion pathway protein G K02457 general secretion pathway protein H K02458 general secretion pathway protein I K02459 general secretion pathway protein J K02460 general secretion pathway protein K K02461 general secretion pathway protein L K02462 general secretion pathway protein M K02463 general secretion pathway protein N K20951 extracellular matrix protein K20952 rugosity and biofilm structure modulator C K20953 rugosity and biofilm structure modulator A K10920 toxin coregulated pilus biosynthesis protein P K10919 toxin coregulated pilus biosynthesis protein H K10921 cholera toxin transcriptional activator K10922 transmembrane regulatory protein ToxS K10923 AraC family transcriptional regulator, TCP pilus virulence regulatory protein K10940 outer membrane protein OmpT K08720 outer membrane protein OmpU K10930 toxin coregulated pilin K10931 toxin coregulated pilus biosynthesis protein B K10932 toxin coregulated pilus biosynthesis outer membrane protein C K10933 toxin coregulated pilus biosynthesis protein D K10934 toxin coregulated pilus biosynthesis protein E K10935 toxin coregulated pilus biosynthesis protein F K10961 toxin coregulated pilus biosynthesis protein I K10962 toxin coregulated pilus biosynthesis protein Q K10963 toxin coregulated pilus biosynthesis protein R K10964 toxin coregulated pilus biosynthesis protein S K10965 toxin coregulated pilus biosynthesis protein T K10936 accessory colonization factor AcfA K10937 accessory colonization factor AcfB K10938 accessory colonization factor AcfC K10939 accessory colonization factor AcfD K10928 cholera enterotoxin subunit A [EC:2.4.2.36] K10929 cholera enterotoxin subunit B K10913 TetR/AcrR family transcriptional regulator, hemagglutinin/protease regulatory protein K08604 vibriolysin [EC:3.4.24.25] K07678 two-component system, NarL family, sensor histidine kinase BarA [EC:2.7.13.3] K07689 two-component system, NarL family, invasion response regulator UvrY K18515 small regulatory RNA CsrB K03563 carbon storage regulator K02777 sugar PTS system EIIA component [EC:2.7.1.-] K02779 glucose PTS system EIICB or EIICBA component [EC:2.7.1.199] K05851 adenylate cyclase, class 1 [EC:4.6.1.1] K10914 CRP/FNR family transcriptional regulator, cyclic AMP receptor protein K03557 Fis family transcriptional regulator, factor for inversion stimulation protein K20954 diguanylate cyclase [EC:2.7.7.65] K20955 diguanylate cyclase [EC:2.7.7.65] K20956 diguanylate cyclase [EC:2.7.7.65] K20957 diguanylate cyclase [EC:2.7.7.65] K20958 diguanylate cyclase [EC:2.7.7.65] K20959 diguanylate cyclase [EC:2.7.7.65] K20960 diguanylate cyclase [EC:2.7.7.65] K20961 diguanylate cyclase [EC:2.7.7.65] K20962 c-di-GMP phosphodiesterase [EC:3.1.4.52] K20963 c-di-GMP phosphodiesterase [EC:3.1.4.52] K13246 c-di-GMP phosphodiesterase [EC:3.1.4.52] K07181 c-di-GMP phosphodiesterase [EC:3.1.4.52] K20964 c-di-GMP phosphodiesterase [EC:3.1.4.52] K20965 c-di-GMP phosphodiesterase [EC:3.1.4.52] K20966 c-di-GMP phosphodiesterase [EC:3.1.4.52] K12276 MSHA biogenesis protein MshE K10924 MSHA pilin protein MshA K10925 MSHA pilin protein MshB K10926 MSHA pilin protein MshC K10927 MSHA pilin protein MshD K10941 sigma-54 dependent transcriptional regulator, flagellar regulatory protein K03092 RNA polymerase sigma-54 factor K03087 RNA polymerase nonessential primary-like sigma factor K10942 two-component system, sensor histidine kinase FlrB [EC:2.7.13.3] K10943 two-component system, response regulator FlrC K02405 RNA polymerase sigma factor FliA 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 ///