Chlamydial protease-like activity factor targets SLC7A11 for degradation to induce ferroptosis and facilitate progeny releases

作者：Wentao Chen, Xin‐zhuan Su, Yuying Pan, Han Zhou, Yidan Gao, Xuemei Wang, Lijuan Jiang, Lihong Zeng, Qingqing Xu, Xueying Yu, Xiaona Yin, Zhanqin Feng, Bao Zhang, Wei Zhao, Yaohua Xue, Lingli Tang, Heping Zheng · 发表于：PLoS Pathogens · 年份：2025 · DOI：10.1371/journal.ppat.1013060 · 被引用次数：7 · 研究领域：Epigenetics and DNA Methylation、Reproductive System and Pregnancy、Urinary and Genital Oncology Studies

Chlamydia trachomatis, the most prevalent bacterial agent of sexually transmitted infections, poses a significant threat to reproductive health. The release of progeny through the orchestrated lysis of host cells plays a crucial role for the development of new infections, though the underlying molecular mechanisms remaining largely unexplored. In this study, we identified a novel mechanism by which Chlamydia induces host cell ferroptosis to facilitate its progeny release. This process involves the degradation of the host protein SLC7A11 by the chlamydial protease-like activity factor (CPAF), resulting in glutathione depletion and subsequent cell death characterized by lipid peroxidation. Infection with a CPAF-deficient strain fails to induce host cell ferroptosis. Notably, inhibiting ferroptosis by vitamin E reduces the Chlamydia burden in low genital tract of mice and trends toward attenuation of pathology. These findings provide new insights into the conserved survival strategies of Chlamydia and understanding of its pathogenesis.