Modulation of host ATP levels by secreted bacterial effectors

Chunlin He, Chuang Li, Yao Liu, Tao-Tao Chen, Chunxiuli Li, Xiao Chu, Shuxin Liu, Lidong Wang, Yong Zhang, Songying Ouyang, Jiaqi Fu, Lei Song () and Zhao-Qing Luo ()
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Chunlin He: The First Hospital of Jilin University
Chuang Li: Purdue University
Yao Liu: Purdue University
Tao-Tao Chen: Fujian Normal University
Chunxiuli Li: The First Hospital of Jilin University
Xiao Chu: The First Hospital of Jilin University
Shuxin Liu: The First Hospital of Jilin University
Lidong Wang: The First Hospital of Jilin University
Yong Zhang: The First Hospital of Jilin University
Songying Ouyang: Fujian Normal University
Jiaqi Fu: The First Hospital of Jilin University
Lei Song: The First Hospital of Jilin University
Zhao-Qing Luo: Purdue University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60046-3

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