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Updated: Jul 9, 2026

Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
A process for controlling intracellular bacterial infections induced by membrane injury
Deepannita Roy1, David R Liston, Vincent J Idone
1Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Abstract:
Strategies for inhibiting phagolysosome fusion are essential for the intracellular survival and replication of many pathogens. We found that the lysosomal synaptotagmin Syt VII is required for a mechanism that promotes phagolysosomal fusion and limits the intracellular growth of pathogenic bacteria. Syt VII was required for a form of Ca2+-dependent phagolysosome fusion that is analogous to Ca2+-regulated exocytosis of lysosomes, which can be triggered by membrane injury. Bacterial type III secretion systems, which permeabilize membranes and cause Ca2+ influx in mammalian cells, promote lysosomal exocytosis and inhibit intracellular survival in Syt VII +/+ but not -/- cells. Thus, the lysosomal repair response can also protect cells against pathogens that trigger membrane permeabilization.
Insights
Lysosomal synaptotagmin Syt VII promotes phagolysosome fusion, limiting bacterial growth. This calcium-dependent mechanism, akin to lysosomal repair, protects cells from pathogens that disrupt membranes.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Phagolysosome fusion is critical for pathogen clearance.
- Inhibiting this fusion aids intracellular pathogen survival.
Purpose of the Study:
- Investigate the role of lysosomal synaptotagmin Syt VII in phagolysosome fusion.
- Determine if Syt VII mediates a cellular defense mechanism against bacterial pathogens.
Main Methods:
- Utilized Syt VII knockout (Syt VII -/-) and wild-type (Syt VII +/+) cells.
- Examined calcium-dependent phagolysosome fusion.
- Assessed intracellular bacterial survival following type III secretion system (T3SS) activation.
Main Results:
- Syt VII is essential for calcium-dependent phagolysosome fusion.
- This fusion mechanism limits intracellular growth of pathogenic bacteria.
- Bacterial T3SS-induced membrane permeabilization and calcium influx trigger lysosomal exocytosis, inhibiting bacterial survival in Syt VII +/+ but not Syt VII -/- cells.
Conclusions:
- Lysosomal Syt VII mediates a repair-like mechanism promoting phagolysosome fusion.
- This pathway restricts intracellular bacterial proliferation.
- Cellular responses to membrane injury can confer resistance to certain bacterial pathogens.
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