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Published on: July 6, 2016
Modulation of host ATP levels by secreted bacterial effectors
Chunlin He1, Chuang Li2, Yao Liu2
1Department of Respiratory Medicine, Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, 130021, China.
Abstract:
Adenosine 5'-triphosphate (ATP) is the currency of energy in cells; it plays essential roles in virtually all cellular processes, ranging from basic metabolism to signaling in development and disease. The opportunistic bacterial pathogen Legionella pneumophila utilizes the Dot/Icm type IV secretion system to deliver over 300 effectors into host cells, some of which utilize ATP to perform biochemical reactions catalyzed by their unique enzymatic activities. However, whether L. pneumophila directly regulates ATP level in host cells is unknown. Here, we discover that the Dot/Icm substrate Ceg14 (Lpg0437, a.k.a. SidL) is an ATP/dATPase, which after being activated by the host protein actin, efficiently converts ATP and dATP into adenosine and deoxyadenosine monophosphate, respectively by a mechanism that requires its S-HxxxE (x, any amino acid) motif. The activity of Ceg14 is regulated by its metaeffector AnkJ (Lpg0436, a.k.a. LegA11), which inhibits its ATPase activity via direct protein-protein interactions. Ceg14 and AnkJ impose temporal regulation of ATP levels in L. pneumophila-infected cells. Our results demonstrate that L. pneumophila modulates the energy level of host cells to create an environment permissive for its growth.
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