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

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

doi:10.1038/s41467-019-11504-2

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.

Highlights

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome
Other unsolved questions include (i) what is the mechanism by which the inducer proteins alleviate the Stl-mediated repression; and (ii) for a specific repressor, is this mechanism conserved among the different inducers? Here, we show the solved structure of the SaPIbov[1] Stl repressor
The Gram-positive phage-inducible chromosomal island (PICI) have developed a unique family of proteins, the Stl repressors, which sense the entry of the PICIhelper phages to the lytic cycle[3,12]

Summary

Introduction

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. The Staphylococcus aureus pathogenicity islands (SaPIs) are the prototypical members of the phage-inducible chromosomal island (PICI) family of mobile genetic elements[1] They are very widespread among the Staphylococci and are responsible for at least one important human disease: toxic shock syndrome[1]. It was initially thought that each of the different Stl repressors could uniquely interact with an individual phageencoded protein, recent work by our laboratories has identified that, instead of targeting a specific phage protein for their derepression, the SaPI-encoded Stl repressors can target multiple phage inducer proteins that perform the same function for the phages, but have completely divergent structures[4]. The Rpr proteins resemble the cI/Cro family of repressors found in temperate phages Both types of repressors prevent excision and replication of the mobile element (PICIs and phages, respectively) by binding to specific regions through an N-terminal HTH DNAbinding domain[1,13]. Induction of the genes under the repression of these regulators should involve the disruption of the dimeric organization by the interaction with a derepressor protein or by the direct cleavage between the N- and

Methods

Results

Conclusion