Letter | Published:

Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands

Nature volume 465, pages 779782 (10 June 2010) | Download Citation

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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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.

Author information

Affiliations

  1. Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA), Apdo. 187, Segorbe, Castellón 12400, Spain

    • María Ángeles Tormo-Más
    • , Ignacio Mir
    •  & José R. Penadés
  2. Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0678, USA

    • Archana Shrestha
    • , Sandra M. Tallent
    •  & Gail E. Christie
  3. Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Barcelona 08193, Spain

    • Susana Campoy
    •  & Jordi Barbé
  4. Instituto de Agrobiotecnología, CSIC-Universidad Pública de Navarra, Pamplona, Navarra 31006, Spain

    • Íñigo Lasa
  5. Skirball Institute Program in Molecular Pathogenesis and Departments of Microbiology and Medicine, New York University Medical Center, 540 First Avenue, New York, New York 10016, USA

    • Richard P. Novick
  6. Departamento de Química, Bioquímica y Biología Molecular, Universidad Cardenal Herrera-CEU, Moncada, Valencia 46113, Spain

    • José R. Penadés

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to José R. Penadés.

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    Supplementary Information

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DOI

https://doi.org/10.1038/nature09065

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