Chlamydial protease-like activity factor targets SLC7A11 for degradation to induce ferroptosis and facilitate progeny releases
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.
Authors
- Yidan Gao (ORCID: https://orcid.org/0000-0002-7519-7229)
- Qingqing Xu (ORCID: https://orcid.org/0000-0002-7703-5872)
- Yaohua Xue (ORCID: https://orcid.org/0000-0002-7334-2541)
- Yuying Pan (ORCID: https://orcid.org/0000-0002-5593-3153)
- Heping Zheng (ORCID: https://orcid.org/0000-0002-9846-975X)
- Xin‐zhuan Su (ORCID: https://orcid.org/0000-0003-3246-3248)
- Lihong Zeng (ORCID: https://orcid.org/0000-0002-3444-8116)
- Bao Zhang (ORCID: https://orcid.org/0000-0003-0459-6406)
- Xuemei Wang
- Wei Zhao (ORCID: https://orcid.org/0000-0002-0750-3132)
- Wentao Chen (ORCID: https://orcid.org/0000-0002-4062-3865)
- Han Zhou (ORCID: https://orcid.org/0000-0002-4899-7837)
- Xueying Yu (ORCID: https://orcid.org/0000-0002-2109-3301)
- Lijuan Jiang (ORCID: https://orcid.org/0000-0002-4659-2457)
- Zhanqin Feng
- Lingli Tang (ORCID: https://orcid.org/0009-0003-8443-9597)
- Xiaona Yin
Institutions
- Central South University (CN)
- Guangdong Provincial Hospital of Traditional Chinese Medicine (CN)
- Second Xiangya Hospital of Central South University (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2025-04-08
- DOI
- https://doi.org/10.1371/journal.ppat.1013060
- Citations
- 5
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Guangzhou Municipal Science and Technology Project
- Basic and Applied Basic Research Foundation of Guangdong Province