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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 publication




Journal article


Mol Cell

Publication Date





309 - 320


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