title: Identification and characterization of cyclic diguanylate signaling systems controlling rugosity in Vibrio cholerae.
abstract: Vibrio cholerae, the causative agent of the disease cholera, can generate rugose variants that have an increased capacity to form biofilms. Rugosity and biofilm formation are critical for the environmental survival and transmission of the pathogen, and these processes are controlled by cyclic diguanylate (c-di-GMP) signaling systems. c-di-GMP is produced by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). Proteins that contain GGDEF domains act as DGCs, whereas proteins that contain EAL or HD-GYP domains act as PDEs. In the V. cholerae genome there are 62 genes that are predicted to encode proteins capable of modulating the cellular c-di-GMP concentration. We previously identified two DGCs, VpvC and CdgA, that can control the switch between smooth and rugose. To identify other c-di-GMP signaling proteins involved in rugosity, we generated in-frame deletion mutants of all genes predicted to encode proteins with GGDEF and EAL domains and then searched for mutants with altered rugosity. In this study, we identified two new genes, cdgG and cdgH, involved in rugosity control. We determined that CdgH acts as a DGC and positively regulates rugosity, whereas CdgG does not have DGC activity and negatively regulates rugosity. In addition, epistasis analysis with CdgG, CdgH, and other DGCs and PDEs controlling rugosity revealed that CdgG and CdgH act in parallel with previously identified c-di-GMP signaling proteins to control rugosity in V. cholerae. We also determined that PilZ domain-containing c-di-GMP binding proteins contribute minimally to rugosity, indicating that there are additional c-di-GMP binding proteins controlling rugosity in V. cholerae.
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: Sinem
authors.initials: S
authors.lastname: Beyhan
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Odell
authors.forename: Fitnat H
authors.initials: FH
authors.lastname: Yildiz
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP
references.citation: Mol Microbiol. 2006 May;60(4):1026-43
references.pmid: 16677312
references.citation: J Infect Dis. 1996 Dec;174(6):1364-8
references.pmid: 8940236
references.citation: J Bacteriol. 2007 Mar;189(6):2319-30
references.pmid: 17220218
references.citation: Appl Environ Microbiol. 1998 Oct;64(10):3648-55
references.pmid: 9758780
references.citation: J Bacteriol. 2003 Feb;185(4):1384-90
references.pmid: 12562809
references.citation: J Biol Chem. 2007 Apr 27;282(17):12860-70
references.pmid: 17307739
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17084-9
references.pmid: 15569936
references.citation: J Biol Chem. 2005 Sep 2;280(35):30829-37
references.pmid: 15994307
references.citation: Clin Microbiol Rev. 2002 Oct;15(4):757-70
references.pmid: 12364378
references.citation: Mol Microbiol. 2001 Jan;39(2):223-35
references.pmid: 11136445
references.citation: J Bacteriol. 2001 Mar;183(5):1716-26
references.pmid: 11160103
references.citation: Mol Microbiol. 2007 Aug;65(4):876-95
references.pmid: 17645452
references.citation: J Bacteriol. 2004 Mar;186(5):1574-8
references.pmid: 14973043
references.citation: J Biol Chem. 2006 Oct 20;281(42):32015-24
references.pmid: 16923812
references.citation: Mol Microbiol. 2004 Apr;52(2):573-87
references.pmid: 15066042
references.citation: Appl Environ Microbiol. 2007 Nov;73(22):7482-7
references.pmid: 17921282
references.citation: J Bacteriol. 2006 Feb;188(3):1049-59
references.pmid: 16428409
references.citation: J Bacteriol. 2007 Jan;189(2):388-402
references.pmid: 17071756
references.citation: Infect Immun. 1999 Mar;67(3):1393-404
references.pmid: 10024587
references.citation: Bioinformatics. 2006 Jan 1;22(1):3-6
references.pmid: 16249258
references.citation: J Bacteriol. 2004 Aug;186(15):4864-74
references.pmid: 15262923
references.citation: J Bacteriol. 1990 Nov;172(11):6557-67
references.pmid: 2172216
references.citation: Mol Microbiol. 2007 Feb;63(4):995-1007
references.pmid: 17233827
references.citation: Microbiology (Reading). 2000 Oct;146 ( Pt 10):2395-2407
references.pmid: 11021916
references.citation: J Biol Chem. 2006 Oct 13;281(41):30310-4
references.pmid: 16920715
references.citation: Dev Cell. 2003 Oct;5(4):647-56
references.pmid: 14536065
references.citation: J Bacteriol. 2006 Apr;188(7):2681-91
references.pmid: 16547056
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1301-14
references.pmid: 9841673
references.citation: FEMS Microbiol Lett. 2001 Sep 11;203(1):11-21
references.pmid: 11557134
references.citation: Mol Microbiol. 2008 Jul;69(2):376-89
references.pmid: 18485075
references.citation: Nature. 1987 Jan 15-21;325(6101):279-81
references.pmid: 18990795
references.citation: Infect Immun. 2008 Apr;76(4):1617-27
references.pmid: 18227161
references.citation: Mol Microbiol. 2006 Apr;60(2):331-48
references.pmid: 16573684
references.citation: J Bacteriol. 2005 Jul;187(14):4774-81
references.pmid: 15995192
references.citation: Infect Immun. 2005 Sep;73(9):5873-82
references.pmid: 16113306
references.citation: Mol Microbiol. 2003 Oct;50(1):101-4
references.pmid: 14507367
references.citation: Appl Environ Microbiol. 2006 Apr;72(4):2849-55
references.pmid: 16597991
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4028-33
references.pmid: 10097157
references.citation: J Bacteriol. 2005 Nov;187(21):7434-43
references.pmid: 16237027
references.citation: FEMS Microbiol Lett. 2003 Oct 10;227(1):113-9
references.pmid: 14568156
references.citation: J Bacteriol. 2007 Nov;189(22):8165-78
references.pmid: 17586641
references.citation: J Bacteriol. 2007 Feb;189(3):717-29
references.pmid: 17122338
references.citation: J Bacteriol. 2006 May;188(10):3600-13
references.pmid: 16672614
references.citation: Genes Dev. 2006 Sep 15;20(18):2605-17
references.pmid: 16980588
references.citation: J Bacteriol. 2005 Mar;187(5):1792-8
references.pmid: 15716451
references.citation: Mol Microbiol. 2002 Jul;45(2):471-83
references.pmid: 12123457
references.citation: Science. 2008 Jul 18;321(5887):411-3
references.pmid: 18635805
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4112-7
references.pmid: 17360486
references.citation: Mol Microbiol. 2004 Jul;53(2):497-515
references.pmid: 15228530
references.citation: Mol Microbiol. 2005 Jul;57(2):420-33
references.pmid: 15978075
references.citation: Microbiology (Reading). 2007 Apr;153(Pt 4):980-994
references.pmid: 17379708
references.citation: Microbiol Immunol. 2007;51(4):369-79
references.pmid: 17446676
references.citation: Methods Enzymol. 1994;235:386-405
references.pmid: 8057911
references.citation: Gene. 1991 Dec 20;109(1):167-8
references.pmid: 1661697
references.citation: Mol Microbiol. 2007 Sep;65(6):1474-84
references.pmid: 17824927
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6712-7
references.pmid: 16611728
references.citation: Mol Microbiol. 2004 Aug;53(3):857-69
references.pmid: 15255898
references.citation: Curr Opin Microbiol. 2006 Apr;9(2):218-28
references.pmid: 16530465