Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens

Johannes Gregor Matthias Rack, Rosa Morra, Eva Barkauskaite, Rolf Kraehenbuehl, Antonio Ariza, Yue Qu, Mary Ortmayer, Orsolya Leidecker, David R Cameron, Ivan Matic, Anton Y Peleg, David Leys, Ana Traven, Ivan Ahel

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)309-20
Number of pages12
JournalMolecular Cell
Issue number2
Publication statusPublished - 16 Jul 2015


  • Adenosine Diphosphate Ribose
  • Bacterial Proteins
  • Catalytic Domain
  • Crystallography, X-Ray
  • Genes, Bacterial
  • HEK293 Cells
  • Host-Pathogen Interactions
  • Humans
  • Lactobacillales
  • Lipoylation
  • Models, Molecular
  • Operon
  • Oxidative Stress
  • Phylogeny
  • Protein Conformation
  • Sirtuins
  • Staphylococcus aureus
  • Streptococcus pyogenes


Dive into the research topics of 'Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens'. Together they form a unique fingerprint.

Cite this