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Mol Cell. 2015 Jul 16;59(2):309-20. doi: 10.1016/j.molcel.2015.06.013. Epub 2015 Jul 9.

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

Author information

1
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
2
Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
3
Cancer Research UK Manchester Institute, Wilmslow Road, Manchester M20 4BX, UK.
4
Department of Microbiology, Monash University, Malvern East, VIC 3145, Australia.
5
Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany.
6
Department of Infectious Diseases, The Alfred Hospital and Monash University, Malvern East, VIC 3145, Australia.
7
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.
8
Department of Biochemistry and Molecular Biology, Monash University, Malvern East, VIC 3145, Australia.
9
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: ivan.ahel@path.ox.ac.uk.

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.

PMID:
26166706
PMCID:
PMC4518038
DOI:
10.1016/j.molcel.2015.06.013
[Indexed for MEDLINE]
Free PMC Article

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