2. Academic Validation
  3. Chlamydial protease-like activity factor targets SLC7A11 for degradation to induce ferroptosis and facilitate progeny releases

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

  • PLoS Pathog. 2025 Apr 8;21(4):e1013060. doi: 10.1371/journal.ppat.1013060.
Wentao Chen 1 2,  Xin Su 3,  Yuying Pan 1 2,  Han Zhou 1 2,  Yidan Gao 4,  Xuemei Wang 4,  Lijuan Jiang 4,  Lihong Zeng 1 2,  Qingqing Xu 1 2,  Xueying Yu 1 2,  Xiaona Yin 1 2,  Zhanqin Feng 1 2,  Bao Zhang 5,  Wei Zhao 5,  Yaohua Xue 1 2,  Lingli Tang 4,  Heping Zheng 1 2 6
Affiliations

Affiliations

  • 1 Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • 2 Guangzhou Key Laboratory for Sexually Transmitted Diseases Control, Guangzhou, China.
  • 3 Department of Clinical Laboratory, Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, China.
  • 4 Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, China.
  • 5 Guangdong Provincial Key Laboratory of Tropical Disease Research, Key Laboratory of Infectious Diseases Research in South China of Ministry of Education, School of Public Health, Southern Medical University, Guangzhou, China.
  • 6 Institute for Global Health, Southern Medical University, Guangzhou, China.
PMID: 40198689 DOI: 10.1371/journal.ppat.1013060
Abstract

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.

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