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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Dec 19;92(26):12055–12059. doi: 10.1073/pnas.92.26.12055

Cell density control of staphylococcal virulence mediated by an octapeptide pheromone.

G Ji 1, R C Beavis 1, R P Novick 1
PMCID: PMC40295  PMID: 8618843

Abstract

Some bacterial pathogens elaborate and secrete virulence factors in response to environmental signals, others in response to a specific host product, and still others in response to no discernible cue. In this study, we have demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself. The octapeptide activates expression of the agr locus, a global regulator of the virulence response. This response involves the reciprocal regulation of genes encoding surface proteins and those encoding secreted virulence factors. As cells enter the postexponential phase, surface protein genes are repressed by agr and secretory protein genes are subsequently activated. The intracellular agr effector is a regulatory RNA, RNAIII, whose transcription is activated by an agr-encoded signal transduction system for which the octapeptide is the ligand.

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Selected References

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  1. Balaban N., Novick R. P. Autocrine regulation of toxin synthesis by Staphylococcus aureus. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1619–1623. doi: 10.1073/pnas.92.5.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chang S., Cohen S. N. High frequency transformation of Bacillus subtilis protoplasts by plasmid DNA. Mol Gen Genet. 1979 Jan 5;168(1):111–115. doi: 10.1007/BF00267940. [DOI] [PubMed] [Google Scholar]
  3. Dunlap P. V., Ray J. M. Requirement for autoinducer in transcriptional negative autoregulation of the Vibrio fischeri luxR gene in Escherichia coli. J Bacteriol. 1989 Jun;171(6):3549–3552. doi: 10.1128/jb.171.6.3549-3552.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hillenkamp F., Karas M., Beavis R. C., Chait B. T. Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem. 1991 Dec 15;63(24):1193A–1203A. doi: 10.1021/ac00024a002. [DOI] [PubMed] [Google Scholar]
  5. Janzon L., Arvidson S. The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus. EMBO J. 1990 May;9(5):1391–1399. doi: 10.1002/j.1460-2075.1990.tb08254.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Janzon L., Löfdahl S., Arvidson S. Identification and nucleotide sequence of the delta-lysin gene, hld, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol Gen Genet. 1989 Nov;219(3):480–485. doi: 10.1007/BF00259623. [DOI] [PubMed] [Google Scholar]
  7. Jones S., Yu B., Bainton N. J., Birdsall M., Bycroft B. W., Chhabra S. R., Cox A. J., Golby P., Reeves P. J., Stephens S. The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa. EMBO J. 1993 Jun;12(6):2477–2482. doi: 10.1002/j.1460-2075.1993.tb05902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kornblum J. S., Projan S. J., Moghazeh S. L., Novick R. P. A rapid method to quantitate non-labeled RNA species in bacterial cells. Gene. 1988;63(1):75–85. doi: 10.1016/0378-1119(88)90547-1. [DOI] [PubMed] [Google Scholar]
  9. Long S. R., Staskawicz B. J. Prokaryotic plant parasites. Cell. 1993 Jun 4;73(5):921–935. doi: 10.1016/0092-8674(93)90271-q. [DOI] [PubMed] [Google Scholar]
  10. Magnuson R., Solomon J., Grossman A. D. Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell. 1994 Apr 22;77(2):207–216. doi: 10.1016/0092-8674(94)90313-1. [DOI] [PubMed] [Google Scholar]
  11. Mekalanos J. J. Environmental signals controlling expression of virulence determinants in bacteria. J Bacteriol. 1992 Jan;174(1):1–7. doi: 10.1128/jb.174.1.1-7.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nixon B. T., Ronson C. W., Ausubel F. M. Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genes ntrB and ntrC. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7850–7854. doi: 10.1073/pnas.83.20.7850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Novick R. P. Genetic systems in staphylococci. Methods Enzymol. 1991;204:587–636. doi: 10.1016/0076-6879(91)04029-n. [DOI] [PubMed] [Google Scholar]
  14. Novick R. P., Projan S. J., Kornblum J., Ross H. F., Ji G., Kreiswirth B., Vandenesch F., Moghazeh S. The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol Gen Genet. 1995 Aug 30;248(4):446–458. doi: 10.1007/BF02191645. [DOI] [PubMed] [Google Scholar]
  15. Novick R. P., Ross H. F., Projan S. J., Kornblum J., Kreiswirth B., Moghazeh S. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 1993 Oct;12(10):3967–3975. doi: 10.1002/j.1460-2075.1993.tb06074.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Novick R. Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology. 1967 Sep;33(1):155–166. doi: 10.1016/0042-6822(67)90105-5. [DOI] [PubMed] [Google Scholar]
  17. O'Callaghan C. H., Morris A., Kirby S. M., Shingler A. H. Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972 Apr;1(4):283–288. doi: 10.1128/aac.1.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Parkinson J. S., Kofoid E. C. Communication modules in bacterial signaling proteins. Annu Rev Genet. 1992;26:71–112. doi: 10.1146/annurev.ge.26.120192.000443. [DOI] [PubMed] [Google Scholar]
  19. Peng H. L., Novick R. P., Kreiswirth B., Kornblum J., Schlievert P. Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol. 1988 Sep;170(9):4365–4372. doi: 10.1128/jb.170.9.4365-4372.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Zhang L., Murphy P. J., Kerr A., Tate M. E. Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones. Nature. 1993 Apr 1;362(6419):446–448. doi: 10.1038/362446a0. [DOI] [PubMed] [Google Scholar]

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