title: Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens.
abstract: Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Johannes Gregor Matthias
authors.initials: JG
authors.lastname: Rack
authors.affiliation: Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
authors.forename: Rosa
authors.initials: R
authors.lastname: Morra
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Barkauskaite
authors.affiliation: Cancer Research UK Manchester Institute, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kraehenbuehl
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ariza
authors.affiliation: Department of Microbiology, Monash University, Malvern East, VIC 3145, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Ortmayer
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Leidecker
authors.affiliation: Department of Infectious Diseases, The Alfred Hospital and Monash University, Malvern East, VIC 3145, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Cameron
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Matic
authors.affiliation: Department of Microbiology, Monash University, Malvern East, VIC 3145, Australia; Department of Infectious Diseases, The Alfred Hospital and Monash University, Malvern East, VIC 3145, Australia.
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
authors.affiliation: Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
authors.forename: David
authors.initials: D
authors.lastname: Leys
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Malvern East, VIC 3145, Australia.
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: ivan.ahel@path.ox.ac.uk.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005798:Genes, Bacterial; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D056546:Lactobacillales / Q000201:enzymology / Q000235:genetics; D054878:Lipoylation; D008958:Models, Molecular; D009876:Operon; D018384:Oxidative Stress; D010802:Phylogeny; D011487:Protein Conformation; D037761:Sirtuins / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D000246:Adenosine Diphosphate Ribose; D037761:Sirtuins