Department of Respiratory Medicine and Center of Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China; Department of Biological Science, Purdue University, West Lafayette, United States
Mowei Zhou
Environmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Marina A Gritsenko
Biological Science Division, Pacific Northwest National Laboratory, Richland, United States
Ernesto S Nakayasu
Biological Science Division, Pacific Northwest National Laboratory, Richland, United States
Department of Respiratory Medicine and Center of Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China
The intracellular pathogen Legionella pneumophila delivers more than 330 effectors into host cells by its Dot/Icm secretion system. Those effectors direct the biogenesis of the Legionella-containing vacuole (LCV) that permits its intracellular survival and replication. It has long been documented that the LCV is associated with mitochondria and a number of Dot/Icm effectors have been shown to target to this organelle. Yet, the biochemical function and host cell target of most of these effectors remain unknown. Here, we found that the Dot/Icm substrate Ceg3 (Lpg0080) is a mono-ADP-ribosyltransferase that localizes to the mitochondria in host cells where it attacks ADP/ATP translocases by ADP-ribosylation, and blunts their ADP/ATP exchange activity. The modification occurs on the second arginine residue in the -RRRMMM- element, which is conserved among all known ADP/ATP carriers from different organisms. Our results reveal modulation of host energy metabolism as a virulence mechanism for L. pneumophila.
