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Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands

Abstract

Staphylococcal superantigen-carrying pathogenicity islands (SaPIs) are discrete, chromosomally integrated units of 15 kilobases that are induced by helper phages to excise and replicate. SaPI DNA is then efficiently encapsidated in phage-like infectious particles, leading to extremely high frequencies of intra- as well as intergeneric transfer1,2,3. In the absence of helper phage lytic growth, the island is maintained in a quiescent prophage-like state by a global repressor, Stl, which controls expression of most of the SaPI genes4. Here we show that SaPI derepression is effected by a specific, non-essential phage protein that binds to Stl, disrupting the Stl–DNA complex and thereby initiating the excision-replication-packaging cycle of the island. Because SaPIs require phage proteins to be packaged5,6, this strategy assures that SaPIs will be transferred once induced. Several different SaPIs are induced by helper phage 80α and, in each case, the SaPI commandeers a different non-essential phage protein for its derepression. The highly specific interactions between different SaPI repressors and helper-phage-encoded antirepressors represent a remarkable evolutionary adaptation involved in pathogenicity island mobilization.

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Figure 1: Induction of SaPIbov1 by different dut alleles.
Figure 2: Phage-inducing proteins bind SaPI-encoded Stl proteins.
Figure 3: The level of SaPIbov1 inducing activity correlates with the central divergent region of Dut.

References

  1. Lindsay, J. A., Ruzin, A., Ross, H. F., Kurepina, N. & Novick, R. P. The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus . Mol. Microbiol. 29, 527–543 (1998)

    CAS  Article  Google Scholar 

  2. Chen, J. & Novick, R. P. Phage-mediated intergeneric transfer of toxin genes. Science 323, 139–141 (2009)

    ADS  CAS  Article  Google Scholar 

  3. Úbeda, C. et al. Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Mol. Microbiol. 56, 836–844 (2005)

    Article  Google Scholar 

  4. Úbeda, C. et al. SaPI mutations affecting replication and transfer and enabling autonomous replication in the absence of helper phage. Mol. Microbiol. 67, 493–503 (2008)

    Article  Google Scholar 

  5. Tallent, S. M., Langston, T. B., Moran, R. G. & Christie, G. E. Transducing particles of Staphylococcus aureus pathogenicity island SaPI1 are comprised of helper phage-encoded proteins. J. Bacteriol. 189, 7520–7524 (2007)

    CAS  Article  Google Scholar 

  6. Tormo, M. A. et al. Staphylococcus aureus pathogenicity island DNA is packaged in particles composed of phage proteins. J. Bacteriol. 190, 2434–2440 (2008)

    CAS  Article  Google Scholar 

  7. Novick, R. P., Penades, J. R. & Christie, G. E. The phage-related chromosomal islands of Gram-positive bacteria. Nature Rev. Microbiol. (in the press). (2010)

  8. Liu, J. et al. Antimicrobial drug discovery through bacteriophage genomics. Nature Biotechnol. 22, 185–191 (2004)

    CAS  Article  Google Scholar 

  9. Charpentier, E. et al. Novel cassette-based shuttle vector system for Gram-positive bacteria. Appl. Environ. Microbiol. 70, 6076–6085 (2004)

    CAS  Article  Google Scholar 

  10. Chan, S. et al. Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism. J. Mol. Biol. 341, 503–517 (2004)

    CAS  Article  Google Scholar 

  11. Ausubel, F. M. et al. Current Protocols in Molecular Biology. (John Wiley & Sons, 1990)

    Google Scholar 

  12. Úbeda, C. et al. SaPI operon I is required for SaPI packaging and is controlled by LexA. Mol. Microbiol. 65, 41–50 (2007)

    Article  Google Scholar 

  13. Ji, G., Beavis, R. & Novick, R. P. Bacterial interference caused by autoinducing peptide variants. Science 276, 2027–2030 (1997)

    CAS  Article  Google Scholar 

  14. Varga, B. et al. Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor. Biochem. Biophys. Res. Commun. 373, 8–13 (2008)

    CAS  Article  Google Scholar 

  15. Arnaud, M., Chastanet, A. & Debarbouille, M. New vector for efficient allelic replacement in naturally nontransformable, low-GC-content, Gram-positive bacteria. Appl. Environ. Microbiol. 70, 6887–6891 (2004)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank J. Casadesús and J. M. Ghigo for comments on the manuscript. This work was supported by grants Consolider-Ingenio CSD2009-00006, BIO2005-08399-C02-02, BIO2008-05284-C02-02 and BIO2008-00642-E/C from the Ministerio de Ciencia e Innovación (MICINN), grants from the Cardenal Herrera-CEU University (PRCEU-UCH25/08 and Copernicus program), from the Conselleria de Agricultura, Pesca i Alimentació (CAPiA) and from the Generalitat Valenciana (ACOMP07/258) to J.R.P.; grants BFU2008-01078 from the MICINN and 2009SGR1106 from the Generalitat de Catalunya to J.B.; NIH grant R21AI067654 and a grant-in-aid from the A. D. Williams Trust and the Baruch Foundation Trust to G.E.C.; and NIH grant R01AI022159-23A2 to R.P.N. Fellowship support for M.A.T.-M. from the Generalitat Valenciana is gratefully acknowledged.

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J.R.P. and G.E.C. conceived and designed the study; M.A.T.-M., I.M., S.M.T. and A.S. isolated and characterized SaPI-resistant phage mutants; M.A.T.-M. and I.M. analysed and characterized the different SaPI-repressor/phage-inducer interactions; S.C. and J.B. performed mobility shift assay experiments; J.R.P., G.E.C., R.P.N., M.A.T.-M., I.M. and I.L. analysed the data; J.R.P., G.E.C. and R.P.N. wrote the manuscript; J.R.P. and G.E.C. supervised the research; J.R.P., G.E.C., J.B., I.L. and R.P.N. obtained funding.

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Correspondence to José R. Penadés.

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The authors declare no competing financial interests.

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This file contains Supplementary Tables 1 - 5, Supplementary Figures 1 - 4 with legends and References. (PDF 2799 kb)

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Tormo-Más, M., Mir, I., Shrestha, A. et al. Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465, 779–782 (2010). https://doi.org/10.1038/nature09065

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