Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1990 Feb;172(2):696–700. doi: 10.1128/jb.172.2.696-700.1990

Coregulation of type 12 M protein and streptococcal C5a peptidase genes in group A streptococci: evidence for a virulence regulon controlled by the virR locus.

W J Simpson 1, D LaPenta 1, C Chen 1, P P Cleary 1
PMCID: PMC208495  PMID: 2404953

Abstract

Group A streptococci express at least two surface-associated virulence factors, the antiphagocytic M protein and the antichemotactic streptococcal C5a peptidase (SCP). Preliminary evidence suggested that the biosynthesis of these two proteins is coordinately controlled and subject to simultaneous phase variation. To explore this possibility further, a series of phase-switching and phase-locked M- variants were assayed for SCP by enzyme-linked immunosorbent assay inhibition and for SCP-specific mRNA by dot blot hybridization. All M- cultures produced diminished amounts of SCP antigen and specific mRNA, whereas revertants produced quantities equivalent to those of the wild-type M+ culture. A phase-locked strain that harbors a deletion in a region upstream of the M12 and SCP genes, termed the virR locus, failed to produce SCP antigen or SCP-specific transcripts. The SCP-specific transcript produced by M+ bacteria was shown by Northern (RNA) blot hybridization to be 4 kilobases in size, distinguishing it from the transcript which encodes M protein. These data demonstrate that phase switching of both SCP and M12 proteins is at the transcriptional level and that expression is under the control of the upstream virR locus. We propose that the genetic determinants of these proteins and of colony morphology comprise a virulence regulon.

Full text

PDF
696

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Caparon M. G., Scott J. R. Identification of a gene that regulates expression of M protein, the major virulence determinant of group A streptococci. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8677–8681. doi: 10.1073/pnas.84.23.8677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen C. C., Cleary P. P. Cloning and expression of the streptococcal C5a peptidase gene in Escherichia coli: linkage to the type 12 M protein gene. Infect Immun. 1989 Jun;57(6):1740–1745. doi: 10.1128/iai.57.6.1740-1745.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cleary P. P. Genetic separation of serum opacity factor from M protein of group A streptococci. Infect Immun. 1978 Oct;22(1):171–175. doi: 10.1128/iai.22.1.171-175.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleary P. P., Johnson Z., Wannamaker L. Genetic instability of M protein and serum opacity factor of group A streptocci: evidence suggesting extrachromosomal control. Infect Immun. 1975 Jul;12(1):109–118. doi: 10.1128/iai.12.1.109-118.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haanes E. J., Cleary P. P. Identification of a divergent M protein gene and an M protein-related gene family in Streptococcus pyogenes serotype 49. J Bacteriol. 1989 Dec;171(12):6397–6408. doi: 10.1128/jb.171.12.6397-6408.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Heath D. G., Cleary P. P. Fc-receptor and M-protein genes of group A streptococci are products of gene duplication. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4741–4745. doi: 10.1073/pnas.86.12.4741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Horstmann R. D., Sievertsen H. J., Knobloch J., Fischetti V. A. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1657–1661. doi: 10.1073/pnas.85.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jacks-Weis J., Kim Y., Cleary P. P. Restricted deposition of C3 on M+ group A streptococci: correlation with resistance to phagocytosis. J Immunol. 1982 Apr;128(4):1897–1902. [PubMed] [Google Scholar]
  9. Miller J. F., Mekalanos J. J., Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989 Feb 17;243(4893):916–922. doi: 10.1126/science.2537530. [DOI] [PubMed] [Google Scholar]
  10. Miller V. L., Mekalanos J. J. Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3471–3475. doi: 10.1073/pnas.81.11.3471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. O'Connor S. P., Cleary P. P. In vivo Streptococcus pyogenes C5a peptidase activity: analysis using transposon- and nitrosoguanidine-induced mutants. J Infect Dis. 1987 Sep;156(3):495–504. doi: 10.1093/infdis/156.3.495. [DOI] [PubMed] [Google Scholar]
  12. O'Connor S. P., Cleary P. P. Localization of the streptococcal C5a peptidase to the surface of group A streptococci. Infect Immun. 1986 Aug;53(2):432–434. doi: 10.1128/iai.53.2.432-434.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Recsei P., Kreiswirth B., O'Reilly M., Schlievert P., Gruss A., Novick R. P. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol Gen Genet. 1986 Jan;202(1):58–61. doi: 10.1007/BF00330517. [DOI] [PubMed] [Google Scholar]
  14. Robbins J. C., Spanier J. G., Jones S. J., Simpson W. J., Cleary P. P. Streptococcus pyogenes type 12 M protein gene regulation by upstream sequences. J Bacteriol. 1987 Dec;169(12):5633–5640. doi: 10.1128/jb.169.12.5633-5640.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Simpson W. J., Cleary P. P. Expression of M type 12 protein by a group A streptococcus exhibits phaselike variation: evidence for coregulation of colony opacity determinants and M protein. Infect Immun. 1987 Oct;55(10):2448–2455. doi: 10.1128/iai.55.10.2448-2455.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Spanier J. G., Jones S. J., Cleary P. Small DNA deletions creating avirulence in Streptococcus pyogenes. Science. 1984 Aug 31;225(4665):935–938. doi: 10.1126/science.6089334. [DOI] [PubMed] [Google Scholar]
  17. Swanson J., Hsu K. C., Gotschlich E. C. Electron microscopic studies on streptococci. I. M antigen. J Exp Med. 1969 Nov 1;130(5):1063–1091. doi: 10.1084/jem.130.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. WILSON A. T. The relative importance of the capsule and the M-antigen in determining colony form of group A streptococci. J Exp Med. 1959 Mar 1;109(3):257–270. doi: 10.1084/jem.109.3.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weiss A. A., Falkow S. Genetic analysis of phase change in Bordetella pertussis. Infect Immun. 1984 Jan;43(1):263–269. doi: 10.1128/iai.43.1.263-269.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wexler D. E., Chenoweth D. E., Cleary P. P. Mechanism of action of the group A streptococcal C5a inactivator. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8144–8148. doi: 10.1073/pnas.82.23.8144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wexler D. E., Nelson R. D., Cleary P. P. Human neutrophil chemotactic response to group A streptococci: bacteria-mediated interference with complement-derived chemotactic factors. Infect Immun. 1983 Jan;39(1):239–246. doi: 10.1128/iai.39.1.239-246.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Winans S. C., Ebert P. R., Stachel S. E., Gordon M. P., Nester E. W. A gene essential for Agrobacterium virulence is homologous to a family of positive regulatory loci. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8278–8282. doi: 10.1073/pnas.83.21.8278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. van de Rijn I., Fischetti V. A. Immunochemical analysis of intact M protein secreted from cell wall-less streptococci. Infect Immun. 1981 Apr;32(1):86–91. doi: 10.1128/iai.32.1.86-91.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES