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

Ciges-Tomas, J. R., Alite, C., Humphrey, S., Donderis, J., Bowring, J. , Salvatella, X., Penadés, J. R. and Marina, A. (2019) The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature. Nature Communications, 10, 3676. (doi:10.1038/s41467-019-11504-2) (PMID:31417084) (PMCID:PMC6695447)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Penades, Professor Jose R and Humphrey, Dr Suzie and Bowring, Janine Zara
Creator Roles:
Penadés, J. R.Conceptualization, Methodology, Investigation, Writing – original draft, Funding acquisition, Resources, Supervision
Humphrey, S.Investigation, Resources
Bowring, J.Investigation, Resources
Authors: Ciges-Tomas, J. R., Alite, C., Humphrey, S., Donderis, J., Bowring, J., Salvatella, X., Penadés, J. R., and Marina, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Communications 10:3676
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
660772Molecular biology of the PICIs, a novel and widespread family of mobile genetic elements involved in bacterial virulenceJose R PenadesMedical Research Council (MRC)MR/M003876/1RI INFECTION IMMUNITY & INFLAMMATION
693781Understanding a novel mechanim involving pathogenity islands in the transfer of unlinked chromosomal virulence genesJose R PenadesBiotechnology and Biological Sciences Research Council (BBSRC)BB/N002873/1RI INFECTION IMMUNITY & INFLAMMATION
3029710Helper and satellite pathogenicity islands: the discovery of two novel subcellular elements with a huge impact on bacterial pathogenesis and evolutionJose R PenadesBiotechnology and Biological Sciences Research Council (BBSRC)BB/S003835/1III - Bacteriology
727241Understanding bacterial host adaptation to combat infectious diseasesJose R PenadesWellcome Trust (WELLCOTR)201531/Z/16/ZRI INFECTION IMMUNITY & INFLAMMATION
687701DUT-SignalJose R PenadesEuropean Research Council (ERC)670932RI INFECTION IMMUNITY & INFLAMMATION