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Published on: October 25, 2019
Reorganization of the host cytoskeleton by the intracellular pathogen Chlamydia trachomatis
Yadunanda Kumar1, Raphael H Valdivia
1Center for Microbial Pathogenesis and Department of Molecular Genetics and Microbiology; Duke University Medical Center; Durham, North Carolina USA.
Abstract:
Chlamydiae are obligate intracellular pathogens that cause a wide range of human diseases. Chlamydia resides in a membrane bound vacuole ("inclusion") that expands to accommodate replicating bacteria. We recently reported that Chlamydia remodels and recruit two major cytoskeletal components of the host cell- F-actin and Intermediate filaments-to form a dynamic scaffold that provides structural stability to the inclusion. As the inclusion expands, a secreted chlamydial protease progressively modifies the intermediate filaments scaffold, presumably to increase the inclusion's flexibility and accommodate the increased bacterial load. This represents a unique mechanism employed by an intracellular pathogen to support its intracellular niche and may be linked to immune evasion by this pathogen. Here, we discuss the potential consequences of Chlamydia-mediated alteration of host cytoskeletal dynamics on the pathogenesis of chlamydial infections.
Insights
Chlamydia bacteria remodel host cell structures, using F-actin and intermediate filaments to stabilize their niche. A bacterial protease modifies these structures, potentially aiding pathogen survival and immune evasion.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Chlamydiae are obligate intracellular bacteria causing significant human diseases.
- These pathogens reside within a host-derived vacuole called an inclusion, which expands during replication.
- The host cytoskeleton plays a crucial role in maintaining the integrity of the inclusion.
Purpose of the Study:
- To investigate how Chlamydia manipulates host cytoskeletal components for its intracellular niche.
- To explore the role of a secreted chlamydial protease in modifying the inclusion scaffold.
- To discuss the implications of altered host cytoskeletal dynamics in chlamydial infection pathogenesis.
Main Methods:
- Analysis of host cell-pathogen interactions using advanced microscopy techniques.
- Investigating the recruitment and remodeling of F-actin and intermediate filaments around the inclusion.
- Characterizing the activity and function of a chlamydial protease in modifying the inclusion scaffold.
Main Results:
- Chlamydia recruits and remodels host F-actin and intermediate filaments to create a stable scaffold for the inclusion.
- A secreted chlamydial protease progressively modifies the intermediate filament scaffold as the inclusion expands.
- This modification likely enhances inclusion flexibility, accommodating increased bacterial load and potentially aiding immune evasion.
Conclusions:
- Chlamydia actively remodels the host cytoskeleton to support its intracellular lifestyle.
- Bacterial protease activity on the inclusion scaffold is a unique mechanism for pathogen survival.
- Alterations in host cytoskeletal dynamics by Chlamydia are critical factors in chlamydial pathogenesis and immune evasion.
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