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Updated: Mar 2, 2026
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17
Kohei Arasaki1, Yumi Mikami1, Stephanie R Shames2
1Department of Molecular Life Sciences, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Abstract:
During infection of macrophages, the pathogenic bacterium Legionella pneumophila secretes effector proteins that induce the conversion of the plasma membrane-derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole. These ER-like vacuoles are ultimately fused with the ER, where the pathogen replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine protease that targets the mitochondria and their associated membranes. Lpg1137 binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that is known to participate in the regulation of mitochondrial dynamics through interaction with the mitochondrial fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L and other SNAREs in starved cells. Cleavage of syntaxin 17 inhibits not only autophagy but also staurosporine-induced apoptosis occurring in a Bax, Drp1-dependent manner. Thus, L. pneumophila can shut down ER-mitochondria communication through cleavage of syntaxin 17.
Insights
Legionella pneumophila uses the effector Lpg1137 to cleave syntaxin 17, a protein regulating mitochondria. This action disrupts endoplasmic reticulum-mitochondria communication, aiding bacterial survival.
Area of Science:
- Microbiology
- Cell Biology
- Molecular Biology
Background:
- Legionella pneumophila infects macrophages, creating an endoplasmic reticulum (ER)-like vacuole for replication.
- This process involves pathogen-secreted effector proteins that manipulate host cell membranes.
Purpose of the Study:
- To investigate the role of the L. pneumophila effector Lpg1137 in host cell manipulation.
- To determine the molecular targets and mechanisms of Lpg1137 during infection.
Main Methods:
- Biochemical assays to identify Lpg1137's enzymatic activity.
- Analysis of Lpg1137's interaction with host proteins, including syntaxin 17.
- Assessment of the impact of syntaxin 17 cleavage on cellular processes like autophagy and apoptosis.
Main Results:
- Lpg1137 is identified as a serine protease targeting mitochondria.
- Lpg1137 directly binds to and cleaves syntaxin 17, a key SNARE protein.
- Cleavage of syntaxin 17 inhibits both autophagy and Bax/Drp1-dependent apoptosis.
Conclusions:
- L. pneumophila Lpg1137 disrupts ER-mitochondria communication by cleaving syntaxin 17.
- This mechanism allows the bacterium to evade host cell defense mechanisms, including apoptosis.
- The study reveals a novel strategy employed by L. pneumophila to establish infection.
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