Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases

eLife

Marina A Gritsenko¹  Ernesto S Nakayasu¹  Zhao-Qing Luo²  Lei Song³  Jiaqi Fu⁴  Mowei Zhou⁵ 

[1] Biological Science Division, Pacific Northwest National Laboratory, Richland, United States;Department of Biological Science, Purdue University, West Lafayette, 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, Changchun, China;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, Changchun, China;Department of Biological Science, Purdue University, West Lafayette, United States;Environmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, United States;

关键词: type iv secretion;    mART;    ADP-ribosylation;    atp/adp transport;    L. pneumophila;    Dictyostelium;    E. coli;    Human;    S. cerevisiae;    Other;   

DOI  :  10.7554/eLife.73611

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY