Staphylococcus aureus pathogenicity islands (SaPIs) are a family of related 15­17Kb mobile genetic elements that carry and disseminate superantigen and other virulence genes. SaPIs reside passively in the bacterial chromosome, repressed by a master repressor called Stl, encoded by the own SaPI. The key feature of their mobility and spread is the induction by helper phages of their excision, replication, and efficient encapsidation into specific small­headed phage­like infectious particles. After infection or induction of a resident helper phage, SaPIs are de­repressed by the specific protein­protein interaction of phage proteins with Stl. SaPIs have developed a fascinating mechanism to ensure their promiscuous transfer by targeting with the Stl repressor structurally unrelated phage proteins performing the same conserved function. Combining structural biology approach and functional characterization in­vivo and in­vitro we decipher the molecular mechanism of this elegant strategy by which the SaPI hijacks the phage process to sense the starting of the lytic cycle. Our structural studies show that the Stl of the island SaPIbov1 combines a canonic HTH N­terminal domain to bind DNA, and sequentially acquires new domains which act as recognizing modules for the different phage proteins (antirepressors). Our in­vivo and in­vitro data deciphers the molecular mechanism that underlies the interaction between the Stl repressor and different phage coded antirepressors, showing how each Stl module mimics the substrate for each anti­repressor type. The interaction of Stl with different types of anti­repressor always disrupts the Stl dimer, implying the DNA dissociation and SaPI derepression. Our results establish the molecular mechanism of the interaction event that detonates the intra­ and inter­ generic transference of the clinically relevant SaPIs.

1 página con el abstract del póster presentado a 44th FEBS Congress Krakow, Poland. July 6-11, 2019

Peer reviewed