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Published on: October 25, 2019
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis
Inês Serrano Pereira1,2, Sara Vilela Pais2, Vítor Borges3
1Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal.
Insights
The study identified CteG, a type III secretion effector protein from Chlamydia trachomatis, as crucial for bacterial lytic exit. CteG mediates host cell lysis, releasing infectious elementary bodies and is regulated independently of the Pgp4 transcriptional regulator.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Cell Biology
Background:
- Chlamydia trachomatis is a significant human pathogen causing ocular and urogenital infections.
- Type III secretion effectors manipulate host cell processes for chlamydial infectious cycle completion.
- CteG, a previously identified C. trachomatis effector, localizes to the host plasma membrane late in infection.
Purpose of the Study:
- To investigate the role of the CteG effector protein in Chlamydia trachomatis infectious cycle.
- To determine if CteG mediates host cell lysis and bacterial release.
- To elucidate the relationship between CteG and the Pgp4 transcriptional regulator in chlamydial lytic exit.
Main Methods:
- Comparative analysis of wild-type and CteG-deficient C. trachomatis strains in mammalian cell infections.
- Complementation studies using a plasmid-encoded CteG in CteG-deficient strains.
- Assessment of host cell cytotoxicity and infectious chlamydiae release.
- Investigation of CteG production and localization in strains with or without Pgp4.
Main Results:
- CteG deficiency resulted in reduced infectious chlamydiae in the supernatant, indicating impaired lytic exit.
- CteG-deficient cells exhibited reduced host cell cytotoxicity, confirming CteG's role in lytic exit.
- CteG production and localization were independent of the Pgp4 transcriptional regulator.
- A double mutant lacking both CteG and Pgp4 showed a similar cytotoxicity defect as single mutants, suggesting a shared pathway.
Conclusions:
- CteG is the first identified type III secretion effector protein directly involved in mediating host cell lytic exit for Chlamydia trachomatis.
- CteG and Pgp4 likely function within a coordinated regulatory cascade to achieve host cell lysis and release of infectious elementary bodies.
- These findings provide new insights into the sophisticated mechanisms employed by C. trachomatis to complete its infectious cycle and spread.
Abstract:
Chlamydia trachomatis is an obligate intracellular bacterium causing ocular and urogenital infections in humans that are a significant burden worldwide. The completion of its characteristic infectious cycle relies on the manipulation of several host cell processes by numerous chlamydial type III secretion effector proteins. We previously identified the C. trachomatis CteG effector and showed it localizes at the host cell plasma membrane at late stages of infection. Here, we showed that, from 48 h post-infection, mammalian cells infected by wild-type C. trachomatis contained more infectious chlamydiae in the culture supernatant than cells infected by a CteG-deficient strain. This phenotype was CteG-dependent as it could be complemented in cells infected by the CteG-deficient strain carrying a plasmid encoding CteG. Furthermore, we detected a CteG-dependent defect on host cell cytotoxicity, indicating that CteG mediates chlamydial lytic exit. Previous studies showed that Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, also mediates chlamydial lytic exit. However, by using C. trachomatis strains encoding or lacking Pgp4, we showed that production and localization of CteG are not regulated by Pgp4. A C. trachomatis strain lacking both CteG and Pgp4 was as defective in promoting host cell cytotoxicity as mutant strains lacking only CteG or Pgp4. Furthermore, CteG overproduction in a plasmid suppressed the host cell cytotoxic defect of CteG- and Pgp4-deficient chlamydiae. Overall, we revealed the first chlamydial type III secretion effector involved in host cell lytic exit. Our data indicates that CteG and Pgp4 participate in a single cascade of events, but involving multiple layers of regulation, leading to lysis of host cells and release of the infectious chlamydiae.
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