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Published on: October 25, 2019
Lysosome repair enables host cell survival and bacterial persistence following Chlamydia trachomatis infection
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. beatty@borcim.wustl.edu
Abstract:
Chlamydiae are obligate intracellular bacteria that replicate within the confines of a membrane-bound vacuole termed the inclusion. The final event in the infectious process is the disruption of the inclusion membrane and release of a multitude of infectious elementary bodies, each capable of eliciting a new infection. Strains of the trachoma biovar of Chlamydia trachomatis are released from the host cell without concomitant host cell death. In this study, analysis of events associated with chlamydial egress revealed that the integrity of the host cell plasma membrane was compromised prior to the inclusion membrane. This disruption was accompanied by the appearance of LAMP-1 at the infected cell surface, implicating lysosome repair of plasma membrane lesions in response to infection. Analysis of the effects of calcium chelators and actin stabilizing agents, indicated calcium-induced actin depolymerization as a requisite to lysosome-plasma membrane fusion and host cell survival. A consequence of this lysosome-mediated repair process, was the retention of residual bacteria within the surviving host cell, providing a unique mechanism for intracellular persistence of C. trachomatis.
Insights
Chlamydia trachomatis evades host cell death by repairing plasma membrane damage with lysosomes. This process retains bacteria, enabling Chlamydia persistence within surviving host cells.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Chlamydiae are obligate intracellular bacteria that replicate within a host-derived vacuole called the inclusion.
- The infectious cycle culminates in the release of elementary bodies, often without host cell death for Chlamydia trachomatis strains.
- The precise mechanisms governing host cell survival during Chlamydia infection remain incompletely understood.
Purpose of the Study:
- To investigate the host cell events preceding Chlamydia trachomatis egress.
- To elucidate the role of host cell repair mechanisms in preventing cell death during infection.
- To identify factors influencing bacterial persistence within surviving host cells.
Main Methods:
- Microscopy and immunofluorescence to track host cell and bacterial components.
- Analysis of host cell membrane integrity using specific markers.
- Biochemical assays to assess the role of calcium and actin dynamics.
Main Results:
- Host cell plasma membrane integrity is compromised before inclusion membrane disruption.
- Lysosome-associated membrane protein 1 (LAMP-1) appears on the cell surface, indicating lysosome involvement in membrane repair.
- Calcium-dependent actin depolymerization is essential for lysosome-plasma membrane fusion and host cell survival.
- Bacterial persistence is facilitated by the retention of residual bacteria within surviving host cells.
Conclusions:
- Chlamydia trachomatis utilizes a host cell repair mechanism involving lysosome-plasma membrane fusion to ensure survival.
- This lysosome-mediated repair process, dependent on calcium and actin dynamics, prevents host cell death.
- The survival strategy allows for intracellular persistence of Chlamydia trachomatis, potentially influencing chronic infections.
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