The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

J. Rafael Ciges-Tomas; Christian Alite; Suzanne Humphrey; J. Donderis; Janine Bowring; Xavier Salvatella; José R. Penadés; Alberto Marina

doi:10.1038/s41467-019-11504-2

The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

J. Rafael Ciges-Tomas, Christian Alite, Suzanne Humphrey, J. Donderis, Janine Bowring, Xavier Salvatella, José R. Penadés, Alberto Marina^*

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure their promiscuous transfer by targeting structurally unrelated proteins performing identically conserved functions for the phage. Here we decipher the molecular mechanism of this elegant strategy by determining the structure of SaPIbov1 Stl alone and in complex with two structurally unrelated dUTPases from different S. aureus phages. Remarkably, SaPIbov1 Stl has evolved different domains implicated in DNA and partner recognition specificity. This work presents the solved structure of a SaPI repressor protein and the discovery of a modular repressor that acquires multispecificity through domain recruiting. Our results establish the mechanism that allows widespread dissemination of SaPIs in nature.

Original language	English
Article number	3676
Number of pages	16
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-11504-2
Publication status	Published - 15 Aug 2019

Funding

This work was supported by grant BIO2016-78571-P from the Ministerio de Economia y Competitividad (Spain) and grant Prometeo II/2014/029 from Valencian Government (Spain) to A.M., and grants MR/M003876/1 and MR/S00940X/1 from the Medical Research Council (UK), BB/N002873/1 and BB/S003835/1 from the Biotechnology and Biological Sciences Research Council (BBSRC, UK), Wellcome Trust 201531/Z/16/Z, and ERC-ADG-2014 Proposal no. 670932 Dut-signal from EU to J.R.P. C.A. and J.R.C were supported by FPI BES-2014-068617 and FPU13/02880 predoctoral fellowships respectively. X-ray diffraction data collection was supported by Diamond Light Source block allocation group (BAG) Proposal MX14739 and MX16258 and Spanish Synchrotron Radiation Facility ALBA Proposal 2016071762 and 2017072262. J.R.P. is thankful to the Royal Society and the Wolfson Foundation for providing him support through a Royal Society Wolfson Fellowship.

Keywords

coevolution
phage biology
x-ray crystallography

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-11504-2Licence: CC BY 4.0

Rafael-Ciges-Tomas-etal-NC-2019-The-structure-of-a-polygamous-repressor-reveals-how-phage-inducible-chromosomal-islands-spreadFinal published version, 2.96 MBLicence: CC BY 4.0

Cite this

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title = "The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature",

abstract = "Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure their promiscuous transfer by targeting structurally unrelated proteins performing identically conserved functions for the phage. Here we decipher the molecular mechanism of this elegant strategy by determining the structure of SaPIbov1 Stl alone and in complex with two structurally unrelated dUTPases from different S. aureus phages. Remarkably, SaPIbov1 Stl has evolved different domains implicated in DNA and partner recognition specificity. This work presents the solved structure of a SaPI repressor protein and the discovery of a modular repressor that acquires multispecificity through domain recruiting. Our results establish the mechanism that allows widespread dissemination of SaPIs in nature.",

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T1 - The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

AU - Rafael Ciges-Tomas, J.

AU - Alite, Christian

AU - Humphrey, Suzanne

AU - Donderis, J.

AU - Bowring, Janine

AU - Salvatella, Xavier

AU - Penadés, José R.

AU - Marina, Alberto

PY - 2019/8/15

Y1 - 2019/8/15

N2 - Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure their promiscuous transfer by targeting structurally unrelated proteins performing identically conserved functions for the phage. Here we decipher the molecular mechanism of this elegant strategy by determining the structure of SaPIbov1 Stl alone and in complex with two structurally unrelated dUTPases from different S. aureus phages. Remarkably, SaPIbov1 Stl has evolved different domains implicated in DNA and partner recognition specificity. This work presents the solved structure of a SaPI repressor protein and the discovery of a modular repressor that acquires multispecificity through domain recruiting. Our results establish the mechanism that allows widespread dissemination of SaPIs in nature.

AB - Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure their promiscuous transfer by targeting structurally unrelated proteins performing identically conserved functions for the phage. Here we decipher the molecular mechanism of this elegant strategy by determining the structure of SaPIbov1 Stl alone and in complex with two structurally unrelated dUTPases from different S. aureus phages. Remarkably, SaPIbov1 Stl has evolved different domains implicated in DNA and partner recognition specificity. This work presents the solved structure of a SaPI repressor protein and the discovery of a modular repressor that acquires multispecificity through domain recruiting. Our results establish the mechanism that allows widespread dissemination of SaPIs in nature.

KW - coevolution

KW - phage biology

KW - x-ray crystallography

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JO - Nature Communications

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The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

Abstract

Funding

Keywords

UN SDGs

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