Chlamydia trachomatis plasmid-encoded protein pORF5 activates unfolded protein response to induce autophagy via MAPK/ERK signaling pathway

• Published in: Biochemical and biophysical research communications Vol. 527; no. 3; pp. 805 - 810
• Main Authors: Wen, Yating, Luo, Fangzhen, Zhao, Yuqi, Su, Shengmei, Shu, Mingyi, Li, Zhongyu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.06.2020
• Subjects: Autophagy; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Chlamydia trachomatis; Chlamydia trachomatis - genetics; Chlamydia trachomatis - physiology; Endoplasmic Reticulum Stress; HeLa Cells; Host-Parasite Interactions; Humans; MAP Kinase Signaling System; MAPK/ERK; Plasmids - genetics; Plasmids - physiology; Unfolded Protein Response; Chlamydia trachomatis; MAPK/ERK; Autophagy; Unfolded protein response
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2020.04.117

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular organism that depends on nutrients from the host cell for their replication and proliferation. Therefore, the interaction between this pathogen and host induces sustained endoplasmic reticulum (ER) stress in the infected cells. Unfolded protein response (UPR) has been demonstrated to be activated by chlamydial secreted effectors, allowing host cells to recover from the stressful state. In this study, we attempted to explore the role of the only secreted plasmid-encoded protein pORF5 of C. trachomatis between UPR and autophagy induction. The results showed that three branches of UPR (PERK, IRE1, and ATF6) were activated by pORF5. pORF5-induced autophagy was repressed by UPR inhibitors GSK2606414 and 4μ8C, while the autophagy inhibition was failed to influence pORF5-induced UPR significantly. MAPK/ERK inhibitor PD98059 partially suppressed the pORF5-induced autophagy, but had little effect on UPR, indicating that pORF5 actives UPR to induce autophagy via the MAPK/ERK signaling pathway. These observations provide clues on how the host maintains the cellular homeostasis during C. trachomatis infection. [Display omitted] •Chlamydial plasmid protein pORF5 induces autophagy and unfolded protein response.•Inhibition of the UPR represses autophagy induced by C. trachomatis and pORF5.•MAPK/ERK activation is involved in UPR and autophagy induced by pORF5.