Modulation of host ATP levels by secreted bacterial effectors
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 s...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60046-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2041-1723 |