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.
Subject(s)
DNA-Binding Proteins/genetics , Genomic Islands/genetics , Staphylococcus Phages/genetics , Staphylococcus aureus/genetics , Biological Coevolution , Crystallography, X-Ray , Models, MolecularABSTRACT
Forty-nine patients diagnosed as having gonarthrosis were given intra-articular treatment with hyaluronic acid (Adant or Hyalgan) in a blind randomised study. We concluded that the efficacy with Adant at 3 months after treatment was greater than with Hyalgan (50% versus 21.1%). The maximum improvement with hyaluronic acid was seen at 5 weeks in 75.4% and the adverse effects consisted of pain in the infiltration side which was almost twice as great with Adant (16.3%).