Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

Janine Bowring,Iltyar Medmedov,Jorge Donderis,Elisa Maiques,Ignacio Mir-Sanchis,Christian Alite,José R Penadés,Alberto Marina,Maan M Neamah,J Rafael Ciges-Tomas

doi:10.7554/elife.26487

Abstract

Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature's most fascinating subcellular parasites.

Highlights

The Staphylococcus aureus pathogenicity islands (SaPIs) are the prototypical members of an extremely common and recently identified family of mobile genetic elements, the phage-inducible chromosomal islands (PICIs) (Martınez-Rubio et al, 2017; Penades and Christie, 2015)
What is the mechanism by which the SaPIbov1 repressor interacts with apparently unrelated proteins? Obviously, and since the trimeric and dimeric Duts perform the same biological function, the most likely scenario would be the existence of a conserved domain in the phage-encoded proteins that would be recognised by the SaPIbov1 coded Stl repressor
To know whether similar domains are present in the dimeric Duts, we initially addressed the following question: does the SaPIbov1 Stl interact just with the fNM1 dimeric Dut or can it interact with other phage coded dimeric Duts? To solve this question, we analysed the fO11 dimeric Dut

Summary

Introduction

The Staphylococcus aureus pathogenicity islands (SaPIs) are the prototypical members of an extremely common and recently identified family of mobile genetic elements, the phage-inducible chromosomal islands (PICIs) (Martınez-Rubio et al, 2017; Penades and Christie, 2015). In the presence of another type of mobile genetic element – the bacteriophages – the repressor proteins start to interact with specific proteins encoded by the bacteriophages This allows the pathogenicity islands to become active and spread to other bacteria. The fact that both dimeric and trimeric Duts induce SaPIbov raised the interesting possibility that the Stl repressors could target different phage proteins, significantly increasing the capacity of the SaPIs to be induced and transferred This result raised other interesting questions about the SaPIs: is this phenomenon exclusive of SaPIbov or are other SaPIs induced by unrelated proteins? We have deciphered the molecular mechanism used by the SaPIs to hijack the helper phage machinery in order to get high intra- and inter-generic transference: instead of interacting with specific partners, SaPIs have evolved a fascinating strategy that promotes their high transfer by pirating conserved phage mechanisms

Results

Discussion

Materials and methods

Funding Funder Wellcome