title: Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control.
abstract: Transfer of phage-related pathogenicity islands of Staphylococcus aureus (SaPI-s) was recently reported to be activated by helper phage dUTPases. This is a novel function for dUTPases otherwise involved in preservation of genomic integrity by sanitizing the dNTP pool. Here we investigated the molecular mechanism of the dUTPase-induced gene expression control using direct techniques. The expression of SaPI transfer initiating proteins is repressed by proteins called Stl. We found that Φ11 helper phage dUTPase eliminates SaPIbov1 Stl binding to its cognate DNA by binding tightly to Stl protein. We also show that dUTPase enzymatic activity is strongly inhibited in the dUTPase:Stl complex and that the dUTPase:dUTP complex is inaccessible to the Stl repressor. Our results disprove the previously proposed G-protein-like mechanism of SaPI transfer activation. We propose that the transfer only occurs if dUTP is cleared from the nucleotide pool, a condition promoting genomic stability of the virulence elements.
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary vertessy@mail.bme.hu vertessy.beata@ttk.mta.hu.
authors.forename: Judit E
authors.initials: JE
authors.lastname: Szabó
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Németh
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Papp-Kádár
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Nyíri
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Leveles
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Abris Á
authors.initials: AÁ
authors.lastname: Bendes
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Zagyva
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Róna
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary Doctoral School of Multidisciplinary Medical Science, University of Szeged, Szeged, Hungary.
authors.forename: Hajnalka L
authors.initials: HL
authors.lastname: Pálinkás
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Besztercei
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Olivér
authors.initials: O
authors.lastname: Ozohanics
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Vékey
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Liliom
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary vertessy@mail.bme.hu vertessy.beata@ttk.mta.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Tóth
authors.affiliation: Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary vertessy@mail.bme.hu vertessy.beata@ttk.mta.hu.
authors.forename: Beáta G
authors.initials: BG
authors.lastname: Vértessy
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase