VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1
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Read the article on pubmed.ncbi.nlm.nih.gov ↗Article · May 2019 · 1 min read
In brief
In brief
This study reveals that H. pylori's VacA toxin creates a protected intracellular bacterial reservoir by disrupting the lysosomal calcium channel TRPML1, enabling bacteria to survive antibiotic treatment. Activating TRPML1 with a small molecule agonist restores lysosomal function and eliminates intracellular bacteria, suggesting a novel therapeutic approach for chronic H. pylori infection and gastric cancer prevention.
Written by the GCMD Library team from the article.
Statements in this article
Helicobacter pylori infection is a proven carcinogen for gastric cancer.
VacA promotes more severe disease and gastric colonization in H. pylori infection.
VacA usurps lysosomal and autophagy pathways to generate a protected reservoir for H. pylori that confers bacterial survival in vitro.
A VacA-generated intracellular niche exists in vivo that protects H. pylori from antibiotic treatment and leads to infection recrudescence after therapy.
VacA targets the lysosomal calcium channel TRPML1 to disrupt endolysosomal trafficking.
H. pylori that lack toxigenic VacA colonize enlarged dysfunctional lysosomes in the gastric epithelium of trpml1-null mice, where they are protected from eradication therapy.
A small molecule agonist directed against TRPML1 reversed the toxic effects of VacA on endolysosomal trafficking, culminating in the clearance of intracellular bacteria.
TRPML1 may represent a therapeutic target for chronic H. pylori infection.