Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization

Donderis, J., Bowring, J. , Maiques, E., Ciges-Tomas, J. R., Alite, C., Mehmedov, I., Tormo-Mas, M. A., Penadés, J. R. and Marina, A. (2017) Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization. PLoS Pathogens, 13(9), e1006581. (doi:10.1371/journal.ppat.1006581) (PMID:28892519) (PMCID:PMC5608427)

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Abstract

The dUTPase (Dut) enzymes, encoded by almost all free-living organisms and some viruses, prevent the misincorporation of uracil into DNA. We previously proposed that trimeric Duts are regulatory proteins involved in different cellular processes; including the phage-mediated transfer of the Staphylococcus aureus pathogenicity island SaPIbov1. Recently, it has been shown that the structurally unrelated dimeric Dut encoded by phage ϕNM1 is similarly able to mobilize SaPIbov1, suggesting dimeric Duts could also be regulatory proteins. How this is accomplished remains unsolved. Here, using in vivo, biochemical and structural approaches, we provide insights into the signaling mechanism used by the dimeric Duts to induce the SaPIbov1 cycle. As reported for the trimeric Duts, dimeric Duts contain an extremely variable region, here named domain VI, which is involved in the regulatory capacity of these enzymes. Remarkably, our results also show that the dimeric Dut signaling mechanism is modulated by dUTP, as with the trimeric Duts. Overall, our results demonstrate that although unrelated both in sequence and structure, dimeric and trimeric Duts control SaPI transfer by analogous mechanisms, representing a fascinating example of convergent evolution. This conserved mode of action highlights the biological significance of Duts as regulatory molecules.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bowring, Janine Zara and Penades, Professor Jose R
Authors: Donderis, J., Bowring, J., Maiques, E., Ciges-Tomas, J. R., Alite, C., Mehmedov, I., Tormo-Mas, M. A., Penadés, J. R., and Marina, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2017 Donderis et al.
First Published:First published in PLoS Pathogens 13(9): e1006581
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
687701DUT-SignalJose R PenadesEuropean Research Council (ERC)670932RI INFECTION IMMUNITY & INFLAMMATION