title: The Cpx system regulates virulence gene expression in Vibrio cholerae.
abstract: Bacteria possess signal transduction pathways capable of sensing and responding to a wide variety of signals. The Cpx envelope stress response, composed of the sensor histidine kinase CpxA and the response regulator CpxR, senses and mediates adaptation to insults to the bacterial envelope. The Cpx response has been implicated in the regulation of a number of envelope-localized virulence determinants across bacterial species. Here, we show that activation of the Cpx pathway in Vibrio cholerae El Tor strain C6706 leads to a decrease in expression of the major virulence factors in this organism, cholera toxin (CT) and the toxin-coregulated pilus (TCP). Our results indicate that this occurs through the repression of production of the ToxT regulator and an additional upstream transcription factor, TcpP. The effect of the Cpx response on CT and TCP expression is mostly abrogated in a cyclic AMP receptor protein (CRP) mutant, although expression of the crp gene is unaltered. Since TcpP production is controlled by CRP, our data suggest a model whereby the Cpx response affects CRP function, which leads to diminished TcpP, ToxT, CT, and TCP production.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Acosta
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pukatzki
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada traivio@ualberta.ca.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Raivio
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D009876:Operon; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000201:enzymology* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C085504:CpxR protein, Bacteria; D011494:Protein Kinases
references.citation: Emerg Infect Dis. 2011 Jul;17(7):1161-8
references.pmid: 21762567
references.citation: Cell Host Microbe. 2011 Aug 18;10(2):165-74
references.pmid: 21843873
references.citation: Emerg Infect Dis. 2011 Nov;17(11):2113-21
references.pmid: 22099115
references.citation: J Bacteriol. 2013 Aug;195(15):3486-502
references.pmid: 23729647
references.citation: MBio. 2013;4(5):e00366-13
references.pmid: 23982069
references.citation: Nat Commun. 2014;5:3549
references.pmid: 24686479
references.citation: J Bacteriol. 1999 Nov;181(21):6772-8
references.pmid: 10542180
references.citation: Mol Microbiol. 2000 Jan;35(1):189-203
references.pmid: 10632889
references.citation: Infect Immun. 2000 Mar;68(3):1491-7
references.pmid: 10678965
references.citation: Mol Microbiol. 2000 Sep;37(5):1186-97
references.pmid: 10972835
references.citation: Mol Microbiol. 2000 Oct;38(1):67-84
references.pmid: 11029691
references.citation: Mol Microbiol. 2001 Jul;41(2):393-407
references.pmid: 11489126
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3129-34
references.pmid: 11854465
references.citation: Mol Microbiol. 2002 Mar;43(6):1577-89
references.pmid: 11952906
references.citation: Nature. 2002 Jun 6;417(6889):642-5
references.pmid: 12050664
references.citation: J Biol Chem. 2002 Jul 5;277(27):24155-61
references.pmid: 11973328
references.citation: Mol Microbiol. 2002 Nov;46(4):1135-47
references.pmid: 12421317
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1286-91
references.pmid: 12552086
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2801-6
references.pmid: 12601157
references.citation: J Bacteriol. 2003 Aug;185(16):4908-19
references.pmid: 12897011
references.citation: Microbiology. 2003 Oct;149(Pt 10):2809-17
references.pmid: 14523114
references.citation: Mol Microbiol. 2004 Jul;53(1):129-42
references.pmid: 15225309
references.citation: Infect Immun. 2004 Aug;72(8):4654-61
references.pmid: 15271926
references.citation: Adv Cyclic Nucleotide Res. 1977;8:85-118
references.pmid: 335847
references.citation: Cell. 1987 Jan 30;48(2):271-9
references.pmid: 3802195
references.citation: Microbiol Immunol. 1986;30(11):1075-83
references.pmid: 3543624
references.citation: Proc Natl Acad Sci U S A. 1987 May;84(9):2833-7
references.pmid: 2883655
references.citation: J Bacteriol. 1988 Jan;170(1):439-41
references.pmid: 2826400
references.citation: J Bacteriol. 1988 Jun;170(6):2575-83
references.pmid: 2836362
references.citation: Infect Immun. 1988 Nov;56(11):2822-9
references.pmid: 2902009
references.citation: J Exp Med. 1988 Oct 1;168(4):1487-92
references.pmid: 2902187
references.citation: Cell. 1991 Jan 11;64(1):29-37
references.pmid: 1898871
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5403-7
references.pmid: 2052618
references.citation: Electrophoresis. 1991 Jun;12(6):448-50
references.pmid: 1653699
references.citation: Nature. 2012 Mar 8;483(7388):182-6
references.pmid: 22367545
references.citation: Infect Immun. 2012 May;80(5):1766-72
references.pmid: 22331433
references.citation: Infect Immun. 2013 Mar;81(3):884-95
references.pmid: 23297386
references.citation: Gene. 1993 Jan 15;123(1):81-6
references.pmid: 8423007
references.citation: Gene. 1993 Sep 30;132(1):101-6
references.pmid: 8406031
references.citation: Methods Enzymol. 1994;235:517-26
references.pmid: 8057923
references.citation: Infect Immun. 2014 Jul;82(7):2980-91
references.pmid: 24799626
references.citation: J Bacteriol. 2014 Dec;196(24):4229-38
references.pmid: 25246476
references.citation: J Bacteriol. 2015 Jan;197(2):262-76
references.pmid: 25368298
references.citation: Mol Microbiol. 1994 Oct;14(1):17-29
references.pmid: 7830555
references.citation: Clin Microbiol Rev. 1995 Jan;8(1):48-86
references.pmid: 7704895
references.citation: EMBO J. 1995 Apr 18;14(8):1664-73
references.pmid: 7737119
references.citation: J Bacteriol. 1995 Jul;177(14):4121-30
references.pmid: 7608087
references.citation: J Bacteriol. 1995 Sep;177(17):5062-9
references.pmid: 7665485
references.citation: Plasmid. 1996 Jan;35(1):1-13
references.pmid: 8693022
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7991-5
references.pmid: 8755590
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):265-70
references.pmid: 8990197
references.citation: Mol Microbiol. 1997 Jan;23(2):323-31
references.pmid: 9044266
references.citation: J Mol Biol. 1997 Jun 13;269(3):301-12
references.pmid: 9199401
references.citation: Mol Microbiol. 1997 Sep;25(6):1003-9
references.pmid: 9350858
references.citation: Mol Microbiol. 1997 Sep;25(6):1099-111
references.pmid: 9350866
references.citation: J Bacteriol. 1997 Dec;179(24):7724-33
references.pmid: 9401031
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):730-4
references.pmid: 9435261
references.citation: J Bacteriol. 1998 Jul;180(14):3522-8
references.pmid: 9657992
references.citation: Mol Microbiol. 1998 Jul;29(1):235-46
references.pmid: 9701817
references.citation: Mol Microbiol. 1999 Feb;31(3):763-71
references.pmid: 10048021
references.citation: Curr Opin Microbiol. 1999 Apr;2(2):159-65
references.pmid: 10322173
references.citation: J Bacteriol. 1999 Jul;181(14):4250-6
references.pmid: 10400582
references.citation: J Bacteriol. 1999 Sep;181(17):5263-72
references.pmid: 10464196
references.citation: Infect Immun. 1999 Oct;67(10):5117-23
references.pmid: 10496885
references.citation: Mol Cell. 2004 Nov 19;16(4):537-47
references.pmid: 15546614
references.citation: J Bacteriol. 2005 Jan;187(1):107-13
references.pmid: 15601694
references.citation: Infect Immun. 2005 Aug;73(8):4488-93
references.pmid: 16040959
references.citation: Nat Rev Microbiol. 2005 Aug;3(8):611-20
references.pmid: 16012515
references.citation: J Bacteriol. 2005 Aug;187(16):5723-31
references.pmid: 16077119
references.citation: Bioinformatics. 2005 Nov 15;21(22):4187-9
references.pmid: 16109747
references.citation: FEMS Microbiol Lett. 2006 Feb;255(2):175-86
references.pmid: 16448494
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1528-33
references.pmid: 16432199
references.citation: J Bacteriol. 2006 Mar;188(6):2214-21
references.pmid: 16513751
references.citation: J Biol Chem. 2007 Mar 23;282(12):8583-93
references.pmid: 17259177
references.citation: Infect Immun. 2007 Aug;75(8):3913-24
references.pmid: 17517869
references.citation: Future Microbiol. 2007 Jun;2(3):335-44
references.pmid: 17661707
references.citation: Microbiology. 2007 Sep;153(Pt 9):2964-75
references.pmid: 17768239
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18229-34
references.pmid: 17986616
references.citation: Cell Host Microbe. 2007 Oct 11;2(4):264-77
references.pmid: 18005744
references.citation: Infect Immun. 2007 Dec;75(12):5542-9
references.pmid: 17875629
references.citation: J Bacteriol. 2008 Mar;190(6):1985-96
references.pmid: 18192394
references.citation: Infect Immun. 2008 Apr;76(4):1465-75
references.pmid: 18227171
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8736-41
references.pmid: 18574146
references.citation: Cell Mol Life Sci. 2008 May;65(9):1347-60
references.pmid: 18278577
references.citation: Adv Exp Med Biol. 2008;631:80-110
references.pmid: 18792683
references.citation: N Engl J Med. 2009 Mar 12;360(11):1060-3
references.pmid: 19279337
references.citation: Cell Host Microbe. 2009 Mar 19;5(3):234-43
references.pmid: 19286133
references.citation: Mol Microbiol. 2009 Jun;72(6):1408-22
references.pmid: 19432797
references.citation: J Bacteriol. 2009 Aug;191(16):5044-56
references.pmid: 19542291
references.citation: Mol Microbiol. 2010 Feb;75(4):1033-46
references.pmid: 20487295
references.citation: Mol Microbiol. 2010 Jun 1;76(5):1095-110
references.pmid: 20444097
references.citation: Mol Microbiol. 2010 Aug;77(3):755-70
references.pmid: 20545841
references.citation: J Bacteriol. 2010 Sep;192(17):4300-10
references.pmid: 20601467
references.citation: Nat Struct Mol Biol. 2010 Oct;17(10):1226-32
references.pmid: 20852644
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19520-4
references.pmid: 20974937
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21128-33
references.pmid: 21084635
references.citation: N Engl J Med. 2011 Jan 6;364(1):33-42
references.pmid: 21142692
references.citation: PLoS Negl Trop Dis. 2011;5(1):e952
references.pmid: 21283614