Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party

Maiques, E., Quiles-Puchalt, N. , Donderis, J., Ciges-Tomas, J. R., Alite, C., Bowring, J. Z. , Humphrey, S., Penadés, J. R. and Marina, A. (2016) Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party. Nucleic Acids Research, 44(11), pp. 5457-5469. (doi:10.1093/nar/gkw317) (PMID:27112567) (PMCID:PMC4914113)

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Abstract

We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Humphrey, Dr Suzanne and Bowring, Janine Zara and Penades, Professor Jose R and Quiles, Miss Nuria
Authors: Maiques, E., Quiles-Puchalt, N., Donderis, J., Ciges-Tomas, J. R., Alite, C., Bowring, J. Z., Humphrey, S., Penadés, J. R., and Marina, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nucleic Acids Research
Publisher:Oxford University Press
ISSN:0305-1048
ISSN (Online):1362-4962
Published Online:25 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Nucleic Acids Research 44(11):5457-5469
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