title: vttRA and vttRB Encode ToxR family proteins that mediate bile-induced expression of type three secretion system genes in a non-O1/non-O139 Vibrio cholerae strain.
abstract: Strain AM-19226 is a pathogenic non-O1/non-O139 serogroup Vibrio cholerae strain that does not encode the toxin-coregulated pilus or cholera toxin but instead causes disease using a type three secretion system (T3SS). Two genes within the T3SS pathogenicity island, herein named vttR(A) (locus tag A33_1664) and vttR(B) (locus tag A33_1675), are predicted to encode proteins that show similarity to the transcriptional regulator ToxR, which is found in all strains of V. cholerae. Strains with a deletion of vttR(A) or vttR(B) showed attenuated colonization in vivo, indicating that the T3SS-encoded regulatory proteins play a role in virulence. lacZ transcriptional reporter fusions to intergenic regions upstream of genes encoding the T3SS structural components identified growth in the presence of bile as a condition that modulates gene expression. Under this condition, VttR(A) and VttR(B) were necessary for maximal gene expression. In contrast, growth in bile did not substantially alter the expression of a reporter fusion to the vopF gene, which encodes an effector protein. Increased vttR(B) reporter fusion activity was observed in a DeltavttR(B) strain background, suggesting that VttR(B) may regulate its own expression. The collective results are consistent with the hypothesis that T3SS-encoded regulatory proteins are essential for pathogenesis and control the expression of selected T3SS genes.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Ashfaqul
authors.initials: A
authors.lastname: Alam
authors.forename: Vincent
authors.initials: V
authors.lastname: Tam
authors.forename: Elaine
authors.initials: E
authors.lastname: Hamilton
authors.forename: Michelle
authors.initials: M
authors.lastname: Dziejman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001646:Bile / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D051379:Mice; D013312:Stress, Physiological; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D044163:Vibrio cholerae non-O1 / Q000187:drug effects* / Q000235:genetics; D014774:Virulence; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; D001616:beta-Galactosidase
references.citation: Annu Rev Microbiol. 2000;54:735-74
references.pmid: 11018143
references.citation: J Bacteriol. 1991 Jul;173(13):4039-48
references.pmid: 1648075
references.citation: Biochim Biophys Acta. 2004 Oct 14;1690(2):93-109
references.pmid: 15469898
references.citation: Infect Immun. 2008 Aug;76(8):3595-605
references.pmid: 18490456
references.citation: Mol Microbiol. 2009 Oct;74(2):347-63
references.pmid: 19703108
references.citation: Curr Issues Intest Microbiol. 2002 Sep;3(2):29-38
references.pmid: 12400636
references.citation: Arch Microbiol. 2006 Sep;186(3):171-81
references.pmid: 16804679
references.citation: J Bacteriol. 1985 Aug;163(2):580-5
references.pmid: 2991197
references.citation: Mol Microbiol. 2006 Nov;62(3):631-40
references.pmid: 16995895
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5403-7
references.pmid: 2052618
references.citation: Infect Immun. 2005 Oct;73(10):6674-9
references.pmid: 16177344
references.citation: Proc Natl Acad Sci U S A. 1984 Jun;81(11):3471-5
references.pmid: 6374658
references.citation: Indian J Med Res. 1996 Feb;103:71-3
references.pmid: 8714141
references.citation: Infect Immun. 1997 Mar;65(3):1131-4
references.pmid: 9038330
references.citation: Curr Opin Microbiol. 2003 Apr;6(2):186-90
references.pmid: 12732310
references.citation: J Mol Biol. 1975 Aug 5;96(2):307-16
references.pmid: 1100846
references.citation: Trends Microbiol. 2003 Nov;11(11):505-10
references.pmid: 14607067
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2123-8
references.pmid: 14766976
references.citation: J Clin Microbiol. 1993 May;31(5):1315-7
references.pmid: 8501234
references.citation: Cell. 1999 Dec 10;99(6):625-34
references.pmid: 10612398
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1301-14
references.pmid: 9841673
references.citation: Lancet. 2004 Jan 17;363(9404):223-33
references.pmid: 14738797
references.citation: J Clin Microbiol. 1996 Oct;34(10):2537-43
references.pmid: 8880516
references.citation: Appl Environ Microbiol. 2008 Sep;74(18):5635-44
references.pmid: 18641168
references.citation: J Mol Biol. 1982 May 5;157(1):105-32
references.pmid: 7108955
references.citation: J Bacteriol. 1999 Mar;181(5):1508-14
references.pmid: 10049382
references.citation: Cell Mol Immunol. 2006 Apr;3(2):115-21
references.pmid: 16696898
references.citation: Epidemiol Infect. 1998 Feb;120(1):1-5
references.pmid: 9528811
references.citation: Infect Immun. 1992 Mar;60(3):864-9
references.pmid: 1311706
references.citation: Infect Immun. 1987 May;55(5):1090-3
references.pmid: 3570456
references.citation: Infect Immun. 2009 Feb;77(2):904-13
references.pmid: 19075025
references.citation: Epidemiol Infect. 1999 Apr;122(2):217-26
references.pmid: 10355785
references.citation: Lancet. 1985 Jul 20;2(8447):163-4
references.pmid: 2862364
references.citation: Infect Immun. 2000 Mar;68(3):1491-7
references.pmid: 10678965
references.citation: Mol Microbiol. 1998 Jul;29(1):235-46
references.pmid: 9701817
references.citation: Cell Microbiol. 2004 Sep;6(9):805-16
references.pmid: 15272862
references.citation: Microbiol Mol Biol Rev. 2005 Dec;69(4):527-43
references.pmid: 16339734
references.citation: Microbiol Mol Biol Rev. 1998 Jun;62(2):379-433
references.pmid: 9618447
references.citation: Infect Immun. 2007 Apr;75(4):1946-53
references.pmid: 17261615
references.citation: Microb Pathog. 2008 Feb;44(2):118-28
references.pmid: 17919878
references.citation: Cell. 1987 Jan 30;48(2):271-9
references.pmid: 3802195
references.citation: Gene. 1989 Apr 15;77(1):61-8
references.pmid: 2744488
references.citation: Epidemiol Rev. 1990;12:179-91
references.pmid: 2286218
references.citation: Curr Opin Microbiol. 2002 Apr;5(2):166-72
references.pmid: 11934613
references.citation: J Clin Microbiol. 1995 Oct;33(10):2715-22
references.pmid: 8567912
references.citation: Biochim Biophys Acta. 2003 Oct 15;1639(2):65-79
references.pmid: 14559113
references.citation: Infect Immun. 2005 Aug;73(8):4488-93
references.pmid: 16040959
references.citation: Infect Immun. 1991 Dec;59(12):4310-7
references.pmid: 1937792
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W690-2
references.pmid: 15980564
references.citation: Curr Microbiol. 2002 Apr;44(4):302-5
references.pmid: 11910503
references.citation: FEMS Immunol Med Microbiol. 2004 Jun 1;41(2):177-85
references.pmid: 15145463
references.citation: Science. 1986 Sep 26;233(4771):1403-8
references.pmid: 3529391
references.citation: FEMS Microbiol Rev. 2002 Jun;26(2):125-39
references.pmid: 12069878
references.citation: J Bacteriol. 1992 Nov;174(21):6807-14
references.pmid: 1400230
references.citation: DNA Cell Biol. 2008 Jul;27(7):347-55
references.pmid: 18462070
references.citation: J Biol Chem. 2008 Jul 4;283(27):18646-54
references.pmid: 18450744
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3465-70
references.pmid: 15728357
references.citation: Infect Immun. 2007 May;75(5):2645-7
references.pmid: 17283087
references.citation: Lancet. 2003 Mar 1;361(9359):743-9
references.pmid: 12620739
references.citation: J Clin Microbiol. 2001 Nov;39(11):4086-92
references.pmid: 11682534
references.citation: Diagn Microbiol Infect Dis. 2004 Aug;49(4):295-7
references.pmid: 15313536
references.citation: Cell Host Microbe. 2007 Apr 19;1(2):95-107
references.pmid: 18005688
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2801-6
references.pmid: 12601157
references.citation: Infect Immun. 1995 Sep;63(9):3642-8
references.pmid: 7642302
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10220-4
references.pmid: 10944196
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3028-33
references.pmid: 15699331
references.citation: Mol Microbiol. 2000 Jan;35(1):189-203
references.pmid: 10632889
references.citation: Infect Immun. 2007 Dec;75(12):5542-9
references.pmid: 17875629
references.citation: Appl Environ Microbiol. 2001 Jun;67(6):2421-9
references.pmid: 11375146
references.citation: Microbes Infect. 2000 Jul;2(8):907-13
references.pmid: 10962274
references.citation: Mol Microbiol. 1999 Jan;31(1):305-17
references.pmid: 9987131
references.citation: Infect Immun. 2000 Dec;68(12):6763-9
references.pmid: 11083793
references.citation: J Bacteriol. 2004 Jun;186(12):3794-805
references.pmid: 15175293
references.citation: J Bacteriol. 1992 Jan;174(1):1-7
references.pmid: 1729202
references.citation: J Bacteriol. 2008 Nov;190(22):7441-52
references.pmid: 18776020