27 Jul 2015

Publication: What modulates the oxidative stress response in pathogenic microorganisms?

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. Oxidative stress has been recognized as a critical factor in human disease, aging, and the immune system function. Rack et al. report a structural and biochemical analysis of a sirtuin/macrodomain system modulating the oxidative stress response in pathogenic microorganisms via reversible protein ADP-ribosylation.

Reference: Rack, J.G.M., Morra, R., Barkauskaite, E., Kraehenbuehl, R., Ariza, A., Qu, Y., Ortmayer, M., Leidecker, O., Cameron, D.R., Matic, I., Peleg, A.Y., Leys, D., Traven, A., Ahel, I. Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens. Molecular Cell 59(2), 16 July 2015, pp.309–320

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