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Updated: May 9, 2025
Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization
Published on: July 28, 2015
Bacterial pathogens hijack host cell peroxisomes for replication vacuole expansion and integrity
Mohammad J Hossain1, Katerina A Romanov1, Jeffrey Jian1
1Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract:
Pathogens manipulate host cell organelles to establish infection. There is extensive evidence of pathogen modulation of the endoplasmic reticulum, Golgi apparatus, mitochondria, endosomes, lysosomes, and nucleus. However, one organelle that has been largely overlooked in connection with bacterial pathogenesis is peroxisomes. Here, we demonstrate that Legionella actively recruits peroxisomes to its replication vacuole using a secreted bacterial effector protein. Defects in peroxisome metabolic function restrict expansion of the Legionella vacuole membrane and cause rupture of this compartment, inhibiting bacterial replication and leading to bacterial degradation. Similarly, peroxisome dysfunction causes Salmonella replication vacuole destabilization and reduced bacterial burden within host cells. Thus, these two intracellular bacterial pathogens exploit host cell peroxisomes to maintain their replication compartments, establishing a critical role for this organelle in disease.
Insights
Pathogenic bacteria like Legionella and Salmonella exploit peroxisomes, vital cell organelles, for replication. Disrupting peroxisome function inhibits bacterial growth and disease progression.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Pathogens extensively manipulate host cell organelles for infection.
- Peroxisomes, crucial metabolic organelles, have been largely overlooked in bacterial pathogenesis.
- Understanding organelle manipulation is key to combating infectious diseases.
Purpose of the Study:
- To investigate the role of peroxisomes in the replication of intracellular bacterial pathogens.
- To determine if pathogens actively recruit peroxisomes to their replication sites.
- To assess the impact of peroxisome dysfunction on bacterial survival and pathogenesis.
Main Methods:
- Utilized genetic manipulation of peroxisome function in host cells.
- Employed microscopy techniques to visualize pathogen-organelle interactions.
- Assessed bacterial replication and vacuole stability upon peroxisome perturbation.
- Investigated the role of bacterial effector proteins in peroxisome recruitment.
Main Results:
- Demonstrated active recruitment of peroxisomes to the *Legionella* replication vacuole via a secreted bacterial effector.
- Showed that defects in peroxisome metabolic function restrict vacuole expansion and lead to vacuole rupture, inhibiting *Legionella* replication.
- Found that peroxisome dysfunction destabilizes the *Salmonella* replication vacuole, reducing bacterial burden.
Conclusions:
- Peroxisomes are actively exploited by *Legionella* and *Salmonella* to maintain their replication compartments.
- Peroxisome metabolic function is critical for the survival and replication of these intracellular pathogens.
- Peroxisomes represent a novel and critical host factor in bacterial disease, offering potential therapeutic targets.
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