1887

Abstract

In an attempt to expand the available knowledge of pathogen–host interactions during growth of (GAS) in nonimmune whole human blood, the extents to which the expression of 51 genes including regulators with known targets, established virulence factors, physiologically important transporters and metabolic enzyme genes was differentially affected in the presence or absence of a functional gene were determined. The results obtained by quantitative real-time PCR using the M49 strain NZ131 showed that CodY influenced GAS gene activity in a dynamic fashion, with differential responses detected for 26 genes and occasionally characterized by discordance in the blood environment compared to laboratory medium. Degenerate derivatives of the recently discovered CodY box potentially serving as a -regulatory element for CodY action were identified in the upstream regions of 15 genes of the NZ131 genome, and these genes featured sequence motifs identical to the NZ131 CodY box in all completely sequenced genomes. As none of these genes represented a genuine virulence factor, it seems likely, therefore, that the observed differential transcription of the majority of virulence genes was caused by indirect actions of CodY as part of a regulatory network.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.46984-0
2007-06-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jmm/56/6/707.html?itemId=/content/journal/jmm/10.1099/jmm.0.46984-0&mimeType=html&fmt=ahah

References

  1. Chaussee M. A., Callegari E. A., Chaussee M. S. 2004; Rgg regulates growth phase-dependent expression of proteins associated with secondary metabolism and stress in Streptococcus pyogenes . J Bacteriol 186:7091–7099 [CrossRef]
    [Google Scholar]
  2. Cunningham M. W. 2000; Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 13:470–511 [CrossRef]
    [Google Scholar]
  3. Degnan B. A., Fontaine M. C., Doebereiner A. H., Lee J. J., Mastroeni P., Dougan G., Goodacre J. A., Kehoe M. A. 2000; Characterization of an isogenic mutant of Streptococcus pyogenes Manfredo lacking the ability to make streptococcal acid glycoprotein. Infect Immun 68:2441–2448 [CrossRef]
    [Google Scholar]
  4. den Hengst C. D., van Hijum S. A. F. T., Geurts J. M. W., Nauta A., Kok J., Kuipers O. P. 2005; The Lactococcus lactis CodY regulon: identification of a conserved cis-regulatory element. J Biol Chem 280:34332–34342 [CrossRef]
    [Google Scholar]
  5. Federle M. J., Scott J. R. 2002; Identification of binding sites for the group A streptococcal global regulator CovR. Mol Microbiol 43:1161–1172 [CrossRef]
    [Google Scholar]
  6. Federle M. J., McIver K. S., Scott J. R. 1999; A response regulator that represses transcription of several virulence operons in the group A streptococcus. J Bacteriol 181:3649–3657
    [Google Scholar]
  7. Ferretti J. J., McShan W. M., Ajdic D., Savic D. J., Savic G., Lyon K., Primeaux C., Sezate S., Suvorov A. N. other authors 2001; Complete genome sequence of an M1 strain of Streptococcus pyogenes . Proc Natl Acad Sci U S A 98:4658–4663 [CrossRef]
    [Google Scholar]
  8. Graham M. R., Smoot L. M., Migliaccio C. A., Virtaneva K., Sturdevant D. E., Porcella S. F., Federle M. J., Adams G. J., Scott J. R., Musser J. M. 2002; Virulence control in group A streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Proc Natl Acad Sci U S A 99:13855–13860 [CrossRef]
    [Google Scholar]
  9. Graham M. R., Virtaneva K., Porcella S. F., Barry W. T., Gowen B. B., Johnson C. R., Wright F. A., Musser J. M. 2005; Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies. Am J Pathol 166:455–465 [CrossRef]
    [Google Scholar]
  10. Gryllos I., Cywes C., Shearer M. H., Cary M., Kennedy R. C., Wessels M. R. 2001; Regulation of capsule gene expression by group A streptococcus during pharyngeal colonization and invasive infection. Mol Microbiol 42:61–74
    [Google Scholar]
  11. Gryllos I., Levin J. C., Wessels M. R. 2003; The CsrR/CsrS two-component system of group A Streptococcus responds to environmental Mg2+ . Proc Natl Acad Sci U S A 100:4227–4232 [CrossRef]
    [Google Scholar]
  12. Guédon E., Serror P., Ehrlich S. D., Renault P., Delorme C. 2001; Pleiotropic transcriptional repressor CodY senses the intracellular pool of branched-chain amino acids in Lactococcus lactis . Mol Microbiol 40:1227–1239 [CrossRef]
    [Google Scholar]
  13. Guédon E., Sperandio B., Pons N., Ehrlich S. D., Renault P. 2005; Overall control of nitrogen metabolism in Lactococcus lactis by CodY, and possible models for CodY regulation in Firmicutes. Microbiology 151:3895–3909 [CrossRef]
    [Google Scholar]
  14. Gusa A. A., Froehlich B. J., Desai D., Stringer V., Scott J. R. 2007; CovR activation of the dipeptide permease promoter (P dppA ) in group A streptococcus. J Bacteriol 189:1407–1416 [CrossRef]
    [Google Scholar]
  15. Hynes W. 2004; Virulence factors of the group A streptococci and genes that regulate their expression. Front Biosci 9:3399–3433 [CrossRef]
    [Google Scholar]
  16. Klenk M., Koczan D., Guthke R., Nakata M., Thiesen H.-J., Podbielski A., Kreikemeyer B. 2005; Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness. Cell Microbiol 7:1237–1250 [CrossRef]
    [Google Scholar]
  17. Kreikemeyer B., Boyle M. D. P., Leonard Buttaro B. A., Heinemann M., Podbielski A. 2001; Group A streptococcal growth phase-associated virulence factor regulation by a novel operon (Fas) with homologies to two-component-type regulators requires a small RNA molecule. Mol Microbiol 39:392–406 [CrossRef]
    [Google Scholar]
  18. Levdikov V. M., Blagova E., Joseph P., Sonenshein A. L., Wilkinson A. J. 2006; The structure of CodY, a GTP- and isoleucine-responsive regulator of stationary phase and virulence in Gram-positive bacteria. J Biol Chem 281:11366–11373 [CrossRef]
    [Google Scholar]
  19. Malke H., Steiner K., McShan W. M., Ferretti J. J. 2006; Linking the nutritional status of Streptococcus pyogenes to alteration of transcriptional gene expression: the action of CodY and RelA. Int J Med Microbiol 296:259–275 [CrossRef]
    [Google Scholar]
  20. Serror P., Sonenshein A. L. 1996; Interaction of CodY, a novel Bacillus subtilis DNA-binding protein, with the dpp promoter region. Mol Microbiol 20:843–852 [CrossRef]
    [Google Scholar]
  21. Shelburne S. A., Sumby P., Sitkiewicz I., Granville C., DeLeo F. R., Musser J. R. 2005; Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva. Proc Natl Acad Sci U S A 102:16037–16042 [CrossRef]
    [Google Scholar]
  22. Shivers R. P., Sonenshein A. L. 2004; Activation of the Bacillus subtilis global regulator CodY by direct interaction with branched-chain amino acids. Mol Microbiol 53:599–611 [CrossRef]
    [Google Scholar]
  23. Sonenshein A. L. 2005; CodY, a global regulator of stationary phase and virulence in Gram-positive bacteria. Curr Opin Microbiol 8:203–207 [CrossRef]
    [Google Scholar]
  24. Steiner K., Malke H. 2001; relA -independent amino acid starvation response network of Streptococcus pyogenes . J Bacteriol 183:7354–7364 [CrossRef]
    [Google Scholar]
  25. Steiner K., Malke H. 2002; Dual control of streptokinase and streptolysin S production by the covRS and fasCAX two-component regulators in Streptococcus dysgalactiae subsp. equisimilis . Infect Immun 70:3627–3636 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.46984-0
Loading
/content/journal/jmm/10.1099/jmm.0.46984-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error