Type VII secretion system extracellular protein B targets STING to evade host anti- Staphylococcus aureus immunity

• 成果类型: Article
• 署名作者: Gao, Lin; Tian, Tian; Xiong, Tingrong; Zhang, Xiaomei; Wang, Ning; Liu, Luxuan; Shi, Yun; Liu, Qiang; Lu, Dongshui; Luo, Ping; Zhang, Weijun; Cheng, Ping; Gou, Qiang; Wang, Yu; Zeng, Hao; Zhang, Xiaokai; Zou, Quanming
• 署名单位: Army Medical University; Army Medical University; Sichuan University; Army Medical University; Army Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12355
• DOI: 10.1073/pnas.2402764121
• 发表日期: 2024-05-28
• 关键词: activation; mechanisms; induction

摘要

Staphylococcus aureus ( S. aureus ) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48 - linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation. Furthermore, EsxB - STING binding appears to interrupt the interaction of 2 vital regulatory proteins with STING: aspartate - histidine - histidine - cysteine domain - containing protein 3 (DHHC3) and TNF receptor - associated factor 6. This persistent dual suppression of STING interactions deregulates intracellular proinflammatory pathways in macrophages, inhibiting STING's palmitoylation at cysteine 91 and its K63 - linked ubiquitination at lysine 83. These findings uncover an immune - evasion mechanism by S. aureus T7SS during intracellular macrophage infection, which has implications for developing effective immunomodulators to combat S. aureus infections.