Abstract
Staphylococcus aureus exoprotein expression is controlled by a global regulon known as agr. This system activates transcription of some target genes and represses transcription of others. Target genes expressed postexponentially such as alpha-hemolysin (hla) are activated by agr; target genes expressed during exponential phase such as protein A (spa) are repressed by agr. A unique feature of the agr system is that this transcriptional regulation is mediated by a 517-nucleotide transcript, RNAIII. While it is clear that agr differentially regulates the expression of exponential and postexponential exoproteins, the precise role of agr in the temporal control of these events has not yet been explored. In this report, we examine the effects of expressing RNAIII, the agr regulator, under the control of the inducible beta-lactamase (bla) promoter at different times in the growth cycle. We confirm previous results showing that agr is required for postexponential-phase expression of hla and further show that a separate postexponential-phase signal independent of agr function is also needed for activation of hla transcription. We also show that in an agr mutant transcription of spa occurs throughout the growth cycle, is inhibited immediately upon induction of RNAIII, and is thus indifferent to the postexponential signal required for hla activation.
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- Abbas-ali B., Coleman G. The characteristics of extracellular protein secretion by Staphylococcus aureus (Wood 46) and their relationship to the regulation of alpha-toxin formation. J Gen Microbiol. 1977 Apr;99(2):277–282. doi: 10.1099/00221287-99-2-277. [DOI] [PubMed] [Google Scholar]
- Albano M., Hahn J., Dubnau D. Expression of competence genes in Bacillus subtilis. J Bacteriol. 1987 Jul;169(7):3110–3117. doi: 10.1128/jb.169.7.3110-3117.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arvidson S., Holme T., Lindholm B. The formation of extracellular proteolytic enzymes by Staphylococcus aureus. Acta Pathol Microbiol Scand B Microbiol Immunol. 1972;80(6):835–844. doi: 10.1111/j.0365-5563.1973.tb00009.x. [DOI] [PubMed] [Google Scholar]
- BERNHEIMER A. W., SCHWARTZ L. L. Isolation and composition of staphylococcal alpha toxin. J Gen Microbiol. 1963 Mar;30:455–468. doi: 10.1099/00221287-30-3-455. [DOI] [PubMed] [Google Scholar]
- Campbell I. M. Secondary metabolism and microbial physiology. Adv Microb Physiol. 1984;25:1–60. doi: 10.1016/s0065-2911(08)60290-8. [DOI] [PubMed] [Google Scholar]
- Carpenter D., Chesbro W. Separable forms of nuclease secreted by Staphylococcus aureus as a function of growth stage. Can J Microbiol. 1974 Mar;20(3):337–345. doi: 10.1139/m74-052. [DOI] [PubMed] [Google Scholar]
- Chater K. F., Bruton C. J., Plaskitt K. A., Buttner M. J., Méndez C., Helmann J. D. The developmental fate of S. coelicolor hyphae depends upon a gene product homologous with the motility sigma factor of B. subtilis. Cell. 1989 Oct 6;59(1):133–143. doi: 10.1016/0092-8674(89)90876-3. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Coleman G., Brown S., Stormonth D. A. A model for the regulation of bacterial extracellular enzyme and toxin biosynthesis. J Theor Biol. 1975 Jul;52(1):143–148. doi: 10.1016/0022-5193(75)90045-4. [DOI] [PubMed] [Google Scholar]
- Czop J. K., Bergdoll M. S. Staphylococcal enterotoxin synthesis during the exponential, transitional, and stationary growth phases. Infect Immun. 1974 Feb;9(2):229–235. doi: 10.1128/iai.9.2.229-235.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engels W., Kamps M., van Boven C. P. Influence of cultivation conditions on the production of staphylocoagulase by Staphylococcus aureus 104. J Gen Microbiol. 1978 Dec;109(2):237–243. doi: 10.1099/00221287-109-2-237. [DOI] [PubMed] [Google Scholar]
- Fairweather N., Kennedy S., Foster T. J., Kehoe M., Dougan G. Expression of a cloned Staphylococcus aureus alpha-hemolysin determinant in Bacillus subtilis and Staphylococcus aureus. Infect Immun. 1983 Sep;41(3):1112–1117. doi: 10.1128/iai.41.3.1112-1117.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horinouchi S., Weisblum B. Nucleotide sequence and functional map of pC194, a plasmid that specifies inducible chloramphenicol resistance. J Bacteriol. 1982 May;150(2):815–825. doi: 10.1128/jb.150.2.815-825.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Kofoid E. C., Parkinson J. S. Transmitter and receiver modules in bacterial signaling proteins. Proc Natl Acad Sci U S A. 1988 Jul;85(14):4981–4985. doi: 10.1073/pnas.85.14.4981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kreiswirth B. N. Genetics and expression of toxic shock syndrome toxin 1: overview. Rev Infect Dis. 1989 Jan-Feb;11 (Suppl 1):S97–100. doi: 10.1093/clinids/11.supplement_1.s97. [DOI] [PubMed] [Google Scholar]
- Kreiswirth B. N., Löfdahl S., Betley M. J., O'Reilly M., Schlievert P. M., Bergdoll M. S., Novick R. P. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature. 1983 Oct 20;305(5936):709–712. doi: 10.1038/305709a0. [DOI] [PubMed] [Google Scholar]
- Mahadevan L. C., Edwards D. R. Signalling and superinduction. Nature. 1991 Feb 28;349(6312):747–748. doi: 10.1038/349747c0. [DOI] [PubMed] [Google Scholar]
- Mahmood R., Khan S. A. Role of upstream sequences in the expression of the staphylococcal enterotoxin B gene. J Biol Chem. 1990 Mar 15;265(8):4652–4656. [PubMed] [Google Scholar]
- Morfeldt E., Janzon L., Arvidson S., Löfdahl S. Cloning of a chromosomal locus (exp) which regulates the expression of several exoprotein genes in Staphylococcus aureus. Mol Gen Genet. 1988 Mar;211(3):435–440. doi: 10.1007/BF00425697. [DOI] [PubMed] [Google Scholar]
- Movitz J. A study on the biosynthesis of protein A in Staphylococcus aureus. Eur J Biochem. 1974 Oct 1;48(1):131–136. doi: 10.1111/j.1432-1033.1974.tb03750.x. [DOI] [PubMed] [Google Scholar]
- Movitz J. Formation of extracellular protein A by Staphylococcus aureus. Eur J Biochem. 1976 Sep;68(1):291–299. doi: 10.1111/j.1432-1033.1976.tb10788.x. [DOI] [PubMed] [Google Scholar]
- Murphy E., Novick R. P. Physical mapping of Staphylococcus aureus penicillinase plasmid pI524: characterization of an invertible region. Mol Gen Genet. 1979 Aug;175(1):19–30. doi: 10.1007/BF00267851. [DOI] [PubMed] [Google Scholar]
- Márquez L. M., Helmann J. D., Ferrari E., Parker H. M., Ordal G. W., Chamberlin M. J. Studies of sigma D-dependent functions in Bacillus subtilis. J Bacteriol. 1990 Jun;172(6):3435–3443. doi: 10.1128/jb.172.6.3435-3443.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicholson W. L., Park Y. K., Henkin T. M., Won M., Weickert M. J., Gaskell J. A., Chambliss G. H. Catabolite repression-resistant mutations of the Bacillus subtilis alpha-amylase promoter affect transcription levels and are in an operator-like sequence. J Mol Biol. 1987 Dec 20;198(4):609–618. doi: 10.1016/0022-2836(87)90204-x. [DOI] [PubMed] [Google Scholar]
- Nishihara T., Freese E. Motility of Bacillus subtilis during growth and sporulation. J Bacteriol. 1975 Jul;123(1):366–371. doi: 10.1128/jb.123.1.366-371.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Novick R. P., Brodsky R. Studies on plasmid replication. I. Plasmid incompatibility and establishment in Staphylococcus aureus. J Mol Biol. 1972 Jul 21;68(2):285–302. doi: 10.1016/0022-2836(72)90214-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Priest F. G. Extracellular enzyme synthesis in the genus Bacillus. Bacteriol Rev. 1977 Sep;41(3):711–753. doi: 10.1128/br.41.3.711-753.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Regassa L. B., Couch J. L., Betley M. J. Steady-state staphylococcal enterotoxin type C mRNA is affected by a product of the accessory gene regulator (agr) and by glucose. Infect Immun. 1991 Mar;59(3):955–962. doi: 10.1128/iai.59.3.955-962.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart G. J., Carlson C. A. The biology of natural transformation. Annu Rev Microbiol. 1986;40:211–235. doi: 10.1146/annurev.mi.40.100186.001235. [DOI] [PubMed] [Google Scholar]
- Stock J. B., Ninfa A. J., Stock A. M. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol Rev. 1989 Dec;53(4):450–490. doi: 10.1128/mr.53.4.450-490.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turner W. H. The effect of medium volume and yeast extract diffusate on delta-hemolysin production by five strains of Staphylococcus aureus. J Appl Bacteriol. 1978 Oct;45(2):291–296. doi: 10.1111/j.1365-2672.1978.tb04225.x. [DOI] [PubMed] [Google Scholar]
- Yoshikawa M., Matsuda F., Naka M., Murofushi E., Tsunematsu Y. Pleiotropic alteration of activities of several toxins and enzymes in mutants of Staphylococcus aureus. J Bacteriol. 1974 Jul;119(1):117–122. doi: 10.1128/jb.119.1.117-122.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]