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Projeto de investigação
Characterization of the interaction between Chlamydia trachomatis and the host cell centrosome
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CteG, a Chlamydia trachomatis protein involved in host cell lytic exit
Publication . Pereira, Inês Isabel Serrano; Mota, Luís
The Phylum Chlamydiae comprises bacteria that only multiply inside eukaryotic host cells, within a membrane-bound vacuole. Among Chlamydiae, the Family Chlamydiaceae includes Chlamydia trachomatis, a major human pathogen causing ocular and genital infections. The characteristic infectious cycle of Chlamydiae involves chlamydial-mediated host cell invasion and egress. Throughout the cycle, Chlamydiae subvert host cell processes through effector proteins delivered into host cells by a type III secretion system. Previously, it was shown that the C. trachomatis CteG effector localizes at the Golgi and plasma membrane of infected cells. Moreover, the first 100 residues of CteG fused to EGFP (EGFP-CteG100) localize at the Golgi upon their ectopic expression in mammalian cells. In this work, we found that CteG mediates C. trachomatis host cell lytic exit. Cells infected by a CteG-deficient strain showed less chlamydiae in the culture supernatant and displayed lower levels of cytotoxicity comparing to cells infected by CteG-producing wild-type and complemented strains. We further showed that CteG and Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, act on the same pathway leading to chlamydial host cell lytic exit. We also found a predicted α-helix on the N-terminal region of CteG that is essential for the localization of ectopically expressed EGFP-CteG100 at the Golgi and plays a role in adequate targeting of CteG to the Golgi and plasma membrane in infected cells. Finally, we identified host cell proteins that may interact with CteG and provided insights into the evolutionary history of cteG by bioinformatics analysis of its homologs in Chlamydiaceae. In summary, this work revealed a role of CteG in C. trachomatis host cell exit, a crucial step of the chlamydial infectious cycle. Together with other findings, this expanded the knowledge on C. trachomatis-host cell interactions and opened avenues for future research.
The Chlamydia trachomatis IncM Protein Interferes with Host Cell Cytokinesis, Centrosome Positioning, and Golgi Distribution and Contributes to the Stability of the Pathogen-Containing Vacuole
Publication . Luís, Maria Pequito; Pereira, Inês Serrano; Bugalhão, Joana N.; Simões, Catarina N.; Mota, Cristiano; Romão, Maria João; Mota, Luís Jaime; DCV - Departamento de Ciências da Vida; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; American Society for Microbiology
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes ocular and urogenital infections in humans. The ability of C. trachomatis to grow intracellularly in a pathogen-containing vacuole (known as an inclusion) depends on chlamydial effector proteins transported into the host cell by a type III secretion system. Among these effectors, several inclusion membrane proteins (Incs) insert in the vacuolar membrane. Here, we show that human cell lines infected by a C. trachomatis strain deficient for Inc CT288/CTL0540 (renamed IncM) displayed less multinucleation than when infected by IncM-producing strains (wild type or complemented). This indicated that IncM is involved in the ability of Chlamydia to inhibit host cell cytokinesis. The capacity of IncM to induce multinucleation in infected cells was shown to be conserved among its chlamydial homologues and appeared to require its two larger regions predicted to be exposed to the host cell cytosol. C. trachomatis-infected cells also displayed IncM-dependent defects in centrosome positioning, Golgi distribution around the inclusion, and morphology and stability of the inclusion. The altered morphology of inclusions containing IncM-deficient C. trachomatis was further affected by depolymerization of host cell microtubules. This was not observed after depolymerization of microfilaments, and inclusions containing wild-type C. trachomatis did not alter their morphology upon depolymerization of microtubules. Overall, these findings suggest that IncM may exert its effector function by acting directly or indirectly on host cell microtubules.
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Fundação para a Ciência e a Tecnologia
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OE
Número da atribuição
SFRH/BD/129756/2017