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Chlamydia trachomatis' struggle to keep its host alive
Barbara S Sixt1, Raphael H Valdivia2, Guido Kroemer3
1INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France. ; Equipe 11 labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris 75006, France. ; Université Paris Descartes, Paris 75006, France. ; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif 94800, France.
Microbial Cell (Graz, Austria)
|March 31, 2017
Summary
Chlamydia trachomatis uses the CpoS protein to control host cell death, preventing premature cell death and ensuring pathogen survival. Loss of CpoS triggers host defenses and reduces infectious particle production.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Chlamydiae are obligate intracellular bacteria with a biphasic developmental cycle, requiring host cell viability for replication.
- Chlamydia trachomatis is a significant human pathogen responsible for sexually transmitted infections.
- Understanding Chlamydia's interaction with host cells is crucial for developing effective treatments.
Purpose of the Study:
- To identify genetic factors in Chlamydia trachomatis that influence host cell survival during infection.
- To investigate the role of the CpoS protein in Chlamydia's intracellular lifestyle and host-pathogen interactions.
Main Methods:
- Forward genetic screen in Chlamydia trachomatis to isolate mutants with altered host cell interactions.
- Utilized advanced genetic tools to link cytotoxicity to the loss of the CpoS protein.
- Assessed host cell responses, bacterial replication, and infectivity in vitro and in vivo mouse models.
Main Results:
- A Chlamydia trachomatis mutant lacking the CpoS protein induced premature host cell death.
- CpoS deficiency led to an exaggerated type-1 interferon response and reduced production of infectious elementary bodies (EBs).
- CpoS-deficient bacteria were cleared more rapidly from the mouse genital tract in vivo.
Conclusions:
- The Chlamydia promoter of survival (CpoS) protein is essential for controlling host cell fate and evading host immune responses.
- Loss of CpoS highlights the role of Chlamydia-mediated host cell control in successful infection.
- CpoS is a potential target for therapeutic strategies against Chlamydia infections.