ENTRY ko02026 Pathway NAME Biofilm formation - Escherichia coli DESCRIPTION Bacteria inhabiting a biofilm are protected from physical stress, antimicrobials, and the host immune system, and thereby cause severe medical, environmental, and technical problems. Biofilm formation in Escherichia coli is regulated by two inversely controlled transcriptional feedforward cascades, the FlhDC/FliA cascade and the sigmaS/MlrA/CsgD cascade, which are active in post-exponentially growing and in stationary phase cells, respectively. Their final outputs, flagella production or the synthesis of the biofilm matrix components curli and cellulose, are mutually exclusive due to complementary sigma factor requirements, the abundant DNA-binding regulator FliZ, and opposite regulation by c-di-GMP. The RNA-binding protein CsrA, a central component of the global regulatory system, inhibits synthesis of the poly-N-acetyl-glucosamine (PGA) exopolysaccharide and glycogen and stimulates the expression of the flagellar master regulator FlhDC. CsrA activity is counteracted by two sRNAs, CsrB and CsrC. The lower figure shows that FlhDC, sigmaS, and CsgD, the transcription factors that control large regulons involved in flagellar and biofilm formation, serve as regulatory hubs for multiple environmental signal integration with a series of sRNAs providing distinct inputs. CLASS Cellular Processes; Cellular community - prokaryotes PATHWAY_MAP ko02026 Biofilm formation - Escherichia coli ORTHOLOGY K02777 sugar PTS system EIIA component [EC:2.7.1.-] K05851 adenylate cyclase, class 1 [EC:4.6.1.1] K10914 CRP/FNR family transcriptional regulator, cyclic AMP receptor protein K02403 flagellar transcriptional activator FlhD K02402 flagellar transcriptional activator FlhC K02398 negative regulator of flagellin synthesis FlgM K02405 RNA polymerase sigma factor FliA K02425 regulator of sigma S factor FliZ K06204 RNA polymerase-binding transcription factor K03087 RNA polymerase nonessential primary-like sigma factor K21084 diguanylate cyclase [EC:2.7.7.65] K21085 diguanylate cyclase [EC:2.7.7.65] K21086 c-di-GMP phosphodiesterase [EC:3.1.4.52] K21087 flagellar brake protein K21088 diguanylate cyclase [EC:2.7.7.65] K14051 c-di-GMP phosphodiesterase Gmr [EC:3.1.4.52] K21089 MerR family transcriptional regulator, activator of the csg genes K04333 LuxR family transcriptional regulator, csgAB operon transcriptional regulatory protein K04335 minor curlin subunit K04334 major curlin subunit K04336 curli production protein K18968 diguanylate cyclase [EC:2.7.7.65] K21090 c-di-GMP phosphodiesterase [EC:3.1.4.52] K00694 cellulose synthase (UDP-forming) [EC:2.4.1.12] K07173 S-ribosylhomocysteine lyase [EC:4.4.1.21] K11531 lsr operon transcriptional repressor K01991 polysaccharide biosynthesis/export protein K12687 antigen 43 K07782 LuxR family transcriptional regulator, quorum-sensing system regulator SdiA 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 K18516 small regulatory RNA CsrC K03563 carbon storage regulator K00975 glucose-1-phosphate adenylyltransferase [EC:2.7.7.27] K00703 starch synthase [EC:2.4.1.21] K00688 glycogen phosphorylase [EC:2.4.1.1] K11935 biofilm PGA synthesis protein PgaA K11931 poly-beta-1,6-N-acetyl-D-glucosamine N-deacetylase [EC:3.5.1.-] K11936 poly-beta-1,6-N-acetyl-D-glucosamine synthase [EC:2.4.1.-] K11937 biofilm PGA synthesis protein PgaD K04761 LysR family transcriptional regulator, hydrogen peroxide-inducible genes activator K18528 small regulatory RNA OxyS K07648 two-component system, OmpR family, aerobic respiration control sensor histidine kinase ArcB [EC:2.7.13.3] K07773 two-component system, OmpR family, aerobic respiration control protein ArcA K18504 small regulatory RNA ArcZ K18502 small regulatory RNA DsrA K07677 two-component system, NarL family, capsular synthesis sensor histidine kinase RcsC [EC:2.7.13.3] K07676 two-component system, NarL family, sensor histidine kinase RcsD [EC:2.7.13.3] K07687 two-component system, NarL family, captular synthesis response regulator RcsB K07781 LuxR family transcriptional regulator, capsular biosynthesis positive transcription factor K18518 small regulatory RNA RprA K03566 LysR family transcriptional regulator, glycine cleavage system transcriptional activator K03567 glycine cleavage system transcriptional repressor K18521 small regulatory RNA GcvB K07638 two-component system, OmpR family, osmolarity sensor histidine kinase EnvZ [EC:2.7.13.3] K07659 two-component system, OmpR family, phosphate regulon response regulator OmpR K18522 small regulatory RNA OmrA K18523 small regulatory RNA OmrB K21091 small regulatory RNA McaS K18509 small regulatory RNA RydC COMPOUND C00037 Glycine C00575 3',5'-Cyclic AMP C01228 Guanosine 3',5'-bis(diphosphate) C04494 Guanosine 3'-diphosphate 5'-triphosphate C16463 3',5'-Cyclic diGMP C21382 R-THMF REFERENCE PMID:25028968 AUTHORS Mika F, Hengge R TITLE Small RNAs in the control of RpoS, CsgD, and biofilm architecture of Escherichia coli. JOURNAL RNA Biol 11:494-507 (2014) DOI:10.4161/rna.28867 REFERENCE PMID:23443158 AUTHORS Mika F, Hengge R TITLE Small Regulatory RNAs in the Control of Motility and Biofilm Formation in E. coli and Salmonella. JOURNAL Int J Mol Sci 14:4560-79 (2013) DOI:10.3390/ijms14034560 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:23178000 AUTHORS Chambers JR, Sauer K TITLE Small RNAs and their role in biofilm formation. JOURNAL Trends Microbiol 21:39-49 (2013) DOI:10.1016/j.tim.2012.10.008 REFERENCE PMID:24724055 AUTHORS Martinez LC, Vadyvaloo V TITLE Mechanisms of post-transcriptional gene regulation in bacterial biofilms. JOURNAL Front Cell Infect Microbiol 4:38 (2014) DOI:10.3389/fcimb.2014.00038 REFERENCE PMID:23023210 AUTHORS Kalia D, Merey G, Nakayama S, Zheng Y, Zhou J, Luo Y, Guo M, Roembke BT, Sintim HO TITLE Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis. JOURNAL Chem Soc Rev 42:305-41 (2013) DOI:10.1039/c2cs35206k REFERENCE PMID:24217225 AUTHORS Seyll E, Van Melderen L TITLE The ribonucleoprotein Csr network. JOURNAL Int J Mol Sci 14:22117-31 (2013) DOI:10.3390/ijms141122117 REFERENCE PMID:18765794 AUTHORS Pesavento C, Becker G, Sommerfeldt N, Possling A, Tschowri N, Mehlis A, Hengge R TITLE Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli. JOURNAL Genes Dev 22:2434-46 (2008) DOI:10.1101/gad.475808 REFERENCE PMID:16427772 AUTHORS Huang YH, Ferrieres L, Clarke DJ TITLE The role of the Rcs phosphorelay in Enterobacteriaceae. JOURNAL Res Microbiol 157:206-12 (2006) DOI:10.1016/j.resmic.2005.11.005 REFERENCE PMID:17557827 AUTHORS Li J, Attila C, Wang L, Wood TK, Valdes JJ, Bentley WE TITLE Quorum sensing in Escherichia coli is signaled by AI-2/LsrR: effects on small RNA and biofilm architecture. JOURNAL J Bacteriol 189:6011-20 (2007) DOI:10.1128/JB.00014-07 REL_PATHWAY ko02024 Quorum sensing ko02040 Flagellar assembly ///