The VarS/VarA two-component system controls the expression of virulence proteins through ToxT regulation Free

Abstract

Although the conditions for inducing virulence protein expression are different, both classical and El Tor biotypes of have been reported to regulate the expression of virulence proteins such as cholera toxin (CT) and toxin-coregulated pili (Tcp) through the ToxR/S/T system. The transcription activator ToxR responds to environmental stimuli such as pH and temperature and activates the second transcriptional regulator ToxT, which upregulates expression of virulence proteins. In addition to the ToxR/S/T signalling system, has been proposed to utilize another two-component system VarS/VarA to modulate expression of virulence genes. Previous study has shown that VarA of the VarS/VarA system is involved in the regulation of virulence proteins in the classical O395 strain; however, no further analysis was performed concerning VarS. In this study, we constructed mutants derived from the classical O395 and El Tor C6706 strains and demonstrated that VarS is also involved in the expression of the virulence proteins CT and Tcp from the classical and El Tor strains. This expression is through regulation of ToxT expression in response to environmental changes due to different toxin-inducing conditions.

Funding
This study was supported by the:
  • Korea National Institute of Health Grant (Award 2006-N00201-00)
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2011-05-01
2024-03-29
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References

  1. Ausubel F. M., Brent R., Kingston R. E., Moore D. E., Seidman J. G., Smith J. A., Struhl K. (editors) ( 1995). Current Protocols in Molecular Biology New York: Wiley;
    [Google Scholar]
  2. Blumer C., Heeb S., Pessi G., Haas D. ( 1999). Global GacA-steered control of cyanide and exoprotease production in Pseudomonas fluorescens involves specific ribosome binding sites. Proc Natl Acad Sci U S A 96:14073–14078 [View Article][PubMed]
    [Google Scholar]
  3. Carroll P. A., Tashima K. T., Rogers M. B., DiRita V. J., Calderwood S. B. ( 1997). Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae. Mol Microbiol 25:1099–1111 [View Article][PubMed]
    [Google Scholar]
  4. Chen X., Schauder S., Potier N., Van Dorsselaer A., Pelczer I., Bassler B. L., Hughson F. M. ( 2002). Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415:545–549 [View Article][PubMed]
    [Google Scholar]
  5. Childers B. M., Weber G. G., Prouty M. G., Castaneda M. M., Peng F., Klose K. E. ( 2007). Identification of residues critical for the function of the Vibrio cholerae virulence regulator ToxT by scanning alanine mutagenesis. J Mol Biol 367:1413–1430 [View Article][PubMed]
    [Google Scholar]
  6. DiRita V. J., Parsot C., Jander G., Mekalanos J. J. ( 1991). Regulatory cascade controls virulence in Vibrio cholerae. Proc Natl Acad Sci U S A 88:5403–5407 [View Article][PubMed]
    [Google Scholar]
  7. DiRita V. J., Neely M., Taylor R. K., Bruss P. M. ( 1996). Differential expression of the ToxR regulon in classical and E1 Tor biotypes of Vibrio cholerae is due to biotype-specific control over toxT expression. Proc Natl Acad Sci U S A 93:7991–7995 [View Article][PubMed]
    [Google Scholar]
  8. Donnenberg M. S., Kaper J. B. ( 1991). Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector. Infect Immun 59:4310–4317[PubMed]
    [Google Scholar]
  9. Faruque S. M., Albert M. J., Mekalanos J. J. ( 1998). Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. Microbiol Mol Biol Rev 62:1301–1314[PubMed]
    [Google Scholar]
  10. Gardel C. L., Mekalanos J. J. ( 1994). Regulation of cholera toxin by temperature, pH, and osmolarity. Methods Enzymol 235:517–526 [View Article][PubMed]
    [Google Scholar]
  11. Gardel C. L., Mekalanos J. J. ( 1996). Alterations in Vibrio cholerae motility phenotypes correlate with changes in virulence factor expression. Infect Immun 64:2246–2255[PubMed]
    [Google Scholar]
  12. Hammer B. K., Bassler B. L. ( 2003). Quorum sensing controls biofilm formation in Vibrio cholerae. Mol Microbiol 50:101–104 [View Article][PubMed]
    [Google Scholar]
  13. Häse C. C., Mekalanos J. J. ( 1998). TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A 95:730–734 [View Article][PubMed]
    [Google Scholar]
  14. Heidelberg J. F., Eisen J. A., Nelson W. C., Clayton R. A., Gwinn M. L., Dodson R. J., Haft D. H., Hickey E. K., Peterson J. D. et al. ( 2000). DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406:477–483 [View Article][PubMed]
    [Google Scholar]
  15. Higgins D. E., DiRita V. J. ( 1994). Transcriptional control of toxT, a regulatory gene in the ToxR regulon of Vibrio cholerae. Mol Microbiol 14:17–29 [View Article][PubMed]
    [Google Scholar]
  16. Jang J., Jung K. T., Yoo C. K., Rhie G. E. ( 2010). Regulation of hemagglutinin/protease expression by the VarS/VarA–CsrA/B/C/D system in Vibrio cholerae. Microb Pathog 48:245–250 [View Article][PubMed]
    [Google Scholar]
  17. Jobling M. G., Holmes R. K. ( 1997). Characterization of hapR, a positive regulator of the Vibrio cholerae HA/protease gene hap, and its identification as a functional homologue of the Vibrio harveyi luxR gene. Mol Microbiol 26:1023–1034 [View Article][PubMed]
    [Google Scholar]
  18. Kaper J. B., Morris J. G. Jr, Levine M. M. ( 1995). Cholera. Clin Microbiol Rev 8:48–86[PubMed]
    [Google Scholar]
  19. Lencer W. I., Tsai B. ( 2003). The intracellular voyage of cholera toxin: going retro. Trends Biochem Sci 28:639–645 [View Article][PubMed]
    [Google Scholar]
  20. Lenz D. H., Bassler B. L. ( 2007). The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing. Mol Microbiol 63:859–871 [View Article][PubMed]
    [Google Scholar]
  21. Lenz D. H., Mok K. C., Lilley B. N., Kulkarni R. V., Wingreen N. S., Bassler B. L. ( 2004). The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118:69–82 [View Article][PubMed]
    [Google Scholar]
  22. Lenz D. H., Miller M. B., Zhu J., Kulkarni R. V., Bassler B. L. ( 2005). CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae. Mol Microbiol 58:1186–1202 [View Article][PubMed]
    [Google Scholar]
  23. Rahme L. G., Tan M. W., Le L., Wong S. M., Tompkins R. G., Calderwood S. B., Ausubel F. M. ( 1997). Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci U S A 94:13245–13250 [View Article][PubMed]
    [Google Scholar]
  24. Reidl J., Klose K. E. ( 2002). Vibrio cholerae and cholera: out of the water and into the host. FEMS Microbiol Rev 26:125–139 [View Article][PubMed]
    [Google Scholar]
  25. Reimmann C., Beyeler M., Latifi A., Winteler H., Foglino M., Lazdunski A., Haas D. ( 1997). The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24:309–319 [View Article][PubMed]
    [Google Scholar]
  26. Simon R., Priefer U., Pühler A. ( 1983). A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in gram negative bacteria. Nat Biotechnol 1:784–791 [View Article]
    [Google Scholar]
  27. Spangler B. D. ( 1992). Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol Rev 56:622–647[PubMed]
    [Google Scholar]
  28. Wong S. M., Carroll P. A., Rahme L. G., Ausubel F. M., Calderwood S. B. ( 1998). Modulation of expression of the ToxR regulon in Vibrio cholerae by a member of the two-component family of response regulators. Infect Immun 66:5854–5861[PubMed]
    [Google Scholar]
  29. Yu R. R., DiRita V. J. ( 1999). Analysis of an autoregulatory loop controlling ToxT, cholera toxin, and toxin-coregulated pilus production in Vibrio cholerae. J Bacteriol 181:2584–2592[PubMed]
    [Google Scholar]
  30. Zhu J., Miller M. B., Vance R. E., Dziejman M., Bassler B. L., Mekalanos J. J. ( 2002). Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A 99:3129–3134 [View Article][PubMed]
    [Google Scholar]
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