CteG, a Chlamydia trachomatis protein involved in host cell lytic exit

• Main Author: Pereira, Inês Isabel Serrano
• Publication Date: 2022
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10362/150109
• topic: Bacterial pathogenesis; pathogen egress; Chlamydia trachomatis; type III secretion; effector proteins; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

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.