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

Research output: Contribution to journalArticle

  • External authors:
  • Johannes Gregor Matthias Rack
  • Eva Barkauskaite
  • Rolf Kraehenbuehl
  • Antonio Ariza
  • Yue Qu
  • Mary Ortmayer
  • Orsolya Leidecker
  • David R Cameron
  • Ivan Matic
  • Anton Y Peleg
  • Ana Traven
  • Ivan Ahel

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)309-20
Number of pages12
JournalMolecular Cell
Volume59
Issue number2
DOIs
StatePublished - 16 Jul 2015