ArticleProceedings of the National Academy of Sciences of the United States of America2016
Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
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- Fighting the invader: strategies against intracellular bacteria.Frontiers in pharmacology · 2026Review
- Phosphatidic acid production on the vacuole harboringProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins.PLoS biology · 2025Article
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition.Nature communications · 2024Article
- Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole.Nature communications · 2024Article
- Breaking the cellular defense: the role of autophagy evasion inFrontiers in cellular and infection microbiology · 2024Article
- Host Lipid Manipulation by Intracellular Bacteria: Moonlighting for Immune Evasion.The Journal of membrane biology · 2023Review
- Effector-mediated subversion of proteasome activator (PA)28αβ enhances host defense against Legionella pneumophila under inflammatory and oxidative stress conditions.PLoS pathogens · 2023Article
- Hiding in the yolk: A unique feature of Legionella pneumophila infection of zebrafish.PLoS pathogens · 2023Article
- Eat or Be Eaten: Strategies Used byInfection and immunity · 2023Review
- Legionella longbeachae effector protein RavZ inhibits autophagy and regulates phagosome ubiquitination during infection.PloS one · 2023Article
- LC3-Associated Phagocytosis in Bacterial Infection.Pathogens (Basel, Switzerland) · 2022Review
- Reversible modification of mitochondrial ADP/ATP translocases by pairedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Unusual Lipid Components ofMetabolites · 2022Article
- The crosstalk between bacteria and host autophagy: host defense or bacteria offense.Journal of microbiology (Seoul, Korea) · 2022Review
- Overview of the Clinical and Molecular Features of Legionella Pneumophila: Focus on Novel Surveillance and Diagnostic Strategies.Antibiotics (Basel, Switzerland) · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 7 institutions in 4 countries.
Funding
Abstract
Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen's Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and -independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.