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Updated: May 2, 2026

Enrichment of Native and Recombinant Extracellular Vesicles of Mycobacteria
Published on: December 8, 2023
PIKfyve mediates the maturation of mycobacteria-containing vesicles
Salomé Muñoz-Sánchez1, Michiel van der Vaart1, Annemarie H Meijer1
1Institute of Biology Leiden, Leiden University, Leiden, Netherlands.
Abstract:
Dynamic interactions between autophagosomes and lysosomes are key to ensuring the trafficking of mycobacteria through the degradative autophagolysosomal pathway. Phosphoinositides (PtdIns), play critical roles in directing the trafficking of pathogens through phagosomal or autophagosomal degradation pathways. Phosphoinositide kinase, FYVE-type zinc finger containing, PIKfyve catalyzes the phosphorylation of PtdIns(3)P to PtdIns(3,5)P2. Generation of PtdIns(3,5)P2 is critical for the maturation of autophagosomes and the proper functioning of lysosomes. The involvement of PIKfyve in immune defense against mycobacterial infections has not been addressed. Here, we studied the role of PIKfyve in Mycobacterium marinum (Mm) infection of zebrafish larvae using two chemical inhibitors of the enzymatic activity of PIKfyve, YM201636 and Apilimod. We demonstrate that PIKfyve is required for Mm-containing vesicle trafficking towards degradative lysosomes. We found that in the infected macrophages, PIKfyve facilitates autophagy pathway activation and (auto)phagosome maturation, and protects against cell death, thus boosting the host immune response against mycobacterial infection. This study links PIKfyve to the autolysosomal defense against a mycobacterial pathogen.
Insights
Phosphoinositide kinase, PIKfyve, is crucial for the host immune response against mycobacterial infections. Inhibiting PIKfyve impairs pathogen trafficking and autophagosome maturation, highlighting its role in cellular defense.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Autophagosome-lysosome interactions are vital for degrading pathogens like mycobacteria.
- Phosphoinositides (PtdIns) regulate pathogen trafficking within cellular degradation pathways.
- PIKfyve kinase generates PtdIns(3,5)P2, essential for autophagosome maturation and lysosome function.
Purpose of the Study:
- To investigate the role of PIKfyve in host defense against Mycobacterium marinum (Mm) infection.
- To determine if PIKfyve activity influences the trafficking and degradation of Mm.
Main Methods:
- Utilized zebrafish larvae infected with Mycobacterium marinum.
- Employed chemical inhibitors (YM201636 and Apilimod) targeting PIKfyve enzymatic activity.
- Analyzed vesicle trafficking, autophagy activation, and phagosome maturation in infected macrophages.
Main Results:
- PIKfyve is essential for trafficking Mm-containing vesicles to degradative lysosomes.
- PIKfyve inhibition disrupts autophagy pathway activation and (auto)phagosome maturation.
- PIKfyve activity protects infected macrophages from cell death, enhancing the immune response.
Conclusions:
- PIKfyve plays a significant role in the cellular immune defense against mycobacterial pathogens.
- The study establishes a link between PIKfyve and the autolysosomal pathway's defense mechanisms against mycobacteria.
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