title: Identification of a diguanylate cyclase and its role in Porphyromonas gingivalis virulence.
abstract: Porphyromonas gingivalis is a Gram-negative obligate anaerobic bacterium and is considered a keystone pathogen in the initiation of periodontitis, one of the most widespread infectious diseases. Bacterial bis-(3'-5') cyclic GMP (cyclic di-GMP [c-di-GMP]) serves as a second messenger and is involved in modulating virulence factors in numerous bacteria. However, the role of this second messenger has not been investigated in P. gingivalis, mainly due to a lack of an annotation regarding diguanylate cyclases (DGCs) in this bacterium. Using bioinformatics tools, we found a protein, PGN_1932, containing a GGDEF domain. A deletion mutation in the pgn_1932 gene had a significant effect on the intracellular c-di-GMP level in P. gingivalis. Genetic analysis showed that expression of the fimA and rgpA genes, encoding the major protein subunit of fimbriae and an arginine-specific proteinase, respectively, was downregulated in the pgn_1932 mutant. Correspondingly, FimA protein production and the fimbrial display on the mutant were significantly reduced. Mutations in the pgn_1932 gene also had a significant impact on the adhesive and invasive capabilities of P. gingivalis, which are required for its pathogenicity. These findings provide evidence that the PGN_1932 protein is both responsible for synthesizing c-di-GMP and involved in biofilm formation and host cell invasion by P. gingivalis by controlling the expression and biosynthesis of FimA.
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Swarnava
authors.initials: S
authors.lastname: Chaudhuri
authors.affiliation: Proteomics Core, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Pratap
authors.affiliation: Proteomics Core, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Paromov
authors.affiliation: Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Chinmay K
authors.initials: CK
authors.lastname: Mantri
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, Tennessee, USA hxie@mmc.edu.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology; D002460:Cell Line; D019295:Computational Biology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase
references.citation: Mol Microbiol. 2007 Aug;65(4):876-95
references.pmid: 17645452
references.citation: BMC Microbiol. 2009 May 26;9:105
references.pmid: 19470157
references.citation: Mol Microbiol. 1998 May;28(3):449-61
references.pmid: 9632250
references.citation: J Gen Microbiol. 1988 Oct;134(10):2713-20
references.pmid: 2908205
references.citation: J Immunol. 2007 Aug 15;179(4):2349-58
references.pmid: 17675496
references.citation: Environ Microbiol. 2004 Jun;6(6):552-67
references.pmid: 15142243
references.citation: J Bacteriol. 1996 May;178(10):2818-24
references.pmid: 8631669
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W362-5
references.pmid: 16845026
references.citation: J Endod. 2009 Jan;35(1):82-5
references.pmid: 19084131
references.citation: Mol Oral Microbiol. 2011 Dec;26(6):388-95
references.pmid: 22053966
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12746-51
references.pmid: 22802636
references.citation: Adv Dent Res. 1988 Nov;2(2):301-3
references.pmid: 2908407
references.citation: Infect Immun. 2006 Oct;74(10):6011-5
references.pmid: 16988281
references.citation: Genome Biol Evol. 2013;5(6):1099-114
references.pmid: 23661565
references.citation: Infect Immun. 1995 Oct;63(10):3878-85
references.pmid: 7558295
references.citation: J Bacteriol. 2008 Nov;190(22):7392-405
references.pmid: 18790873
references.citation: Contrib Microbiol. 2009;16:161-181
references.pmid: 19494585
references.citation: J Bacteriol. 2011 Oct;193(20):5683-91
references.pmid: 21856843
references.citation: Oral Microbiol Immunol. 2000 Dec;15(6):371-7
references.pmid: 11154434
references.citation: Mol Microbiol. 2004 Oct;54(2):546-60
references.pmid: 15469523
references.citation: Nature. 1987 Jan 15-21;325(6101):279-81
references.pmid: 18990795
references.citation: Nucleic Acids Res. 1990 Oct 25;18(20):6069-74
references.pmid: 2235490
references.citation: J Mol Microbiol Biotechnol. 1999 Nov;1(2):303-5
references.pmid: 10943560
references.citation: J Bacteriol. 2005 Jul;187(14):4774-81
references.pmid: 15995192
references.citation: Infect Immun. 1997 Jun;65(6):2265-71
references.pmid: 9169762
references.citation: FEMS Microbiol Lett. 2008 May;282(2):188-95
references.pmid: 18355277
references.citation: J Bacteriol. 2004 May;186(9):2724-34
references.pmid: 15090514
references.citation: Microbiol Res. 2010 Feb 28;165(2):87-96
references.pmid: 19186044
references.citation: FEMS Microbiol Lett. 2007 Aug;273(1):103-8
references.pmid: 17559391
references.citation: Infect Immun. 2005 Sep;73(9):5873-82
references.pmid: 16113306
references.citation: Microbiol Mol Biol Rev. 2013 Mar;77(1):1-52
references.pmid: 23471616
references.citation: J Bacteriol. 2013 Sep;195(17):3897-905
references.pmid: 23794624
references.citation: J Bacteriol. 2006 Apr;188(8):3073-87
references.pmid: 16585767
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1244-63
references.pmid: 9841671
references.citation: Curr Opin Microbiol. 2012 Apr;15(2):140-6
references.pmid: 22226607
references.citation: Mol Microbiol. 2000 Apr;36(1):10-23
references.pmid: 10760159
references.citation: J Dent Res. 2004 Dec;83(12):941-5
references.pmid: 15557402
references.citation: J Bacteriol. 1996 Jan;178(1):46-53
references.pmid: 8550441
references.citation: FEMS Microbiol Lett. 2001 Oct 16;204(1):163-7
references.pmid: 11682196
references.citation: J Bacteriol. 2005 Oct;187(19):6816-23
references.pmid: 16166544
references.citation: Bioinformatics. 2001 Sep;17(9):847-8
references.pmid: 11590104
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W433-7
references.pmid: 17545200
references.citation: Mol Microbiol. 2003 Mar;47(6):1695-708
references.pmid: 12622822
references.citation: DNA Res. 2008 Aug;15(4):215-25
references.pmid: 18524787
references.citation: J Dent Res. 2011 Oct;90(10):1155-63
references.pmid: 21447698
references.citation: Microb Pathog. 2004 Apr;36(4):205-9
references.pmid: 15001226
references.citation: J Bacteriol. 1998 Sep;180(17):4416-25
references.pmid: 9721278
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2839-44
references.pmid: 16477007
references.citation: Infect Immun. 2013 Aug;81(8):2705-13
references.pmid: 23690403
references.citation: J Bacteriol. 2009 Jan;191(1):115-22
references.pmid: 18931136