2. Academic Validation
  3. Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection

Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection

  • Nat Commun. 2023 Jan 30;14(1):478. doi: 10.1038/s41467-023-36123-w.
Shuangshuang Zhao # 1 2,  Qiuping Xu # 3,  Yanqin Cui # 1,  Su Yao 4,  Sihui Jin 3 5,  Qian Zhang 2,  Zeyu Wen 2 5,  Haihua Ruan 6,  Xin Liang 7,  Yanjie Chao 3 5,  Sitang Gong 1,  Philippe Sansonetti 3,  Ke Wei 8,  Hong Tang 9 10,  Yaming Jiu 11 12 13
Affiliations

Affiliations

  • 1 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
  • 2 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 3 CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 4 Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
  • 5 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing, 100049, China.
  • 6 Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
  • 7 Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 8 Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. kewei@tongji.edu.cn.
  • 9 CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. htang@ips.ac.cn.
  • 10 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing, 100049, China. htang@ips.ac.cn.
  • 11 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China. ymjiu@ips.ac.cn.
  • 12 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. ymjiu@ips.ac.cn.
  • 13 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing, 100049, China. ymjiu@ips.ac.cn.
  • # Contributed equally.
PMID: 36717589 DOI: 10.1038/s41467-023-36123-w
Abstract

A variety of intracellular bacteria modulate the host Cytoskeleton to establish subcellular niches for replication. However, the role of intermediate filaments, which are crucial for mechanical strength and resilience of the cell, and in Bacterial vacuole preservation remains unclear. Here, we show that Salmonella effector SopB reorganizes the vimentin network to form cage-like structures that surround Salmonella-containing vacuoles (SCVs). Genetic removal of vimentin markedly disrupts SCV organization, significantly reduces Bacterial replication and cell death. Mechanistically, SopB uses its N-terminal Cdc42-binding domain to interact with and activate Cdc42 GTPase, which in turn recruits vimentin around SCVs. A high-content imaging-based screening identified that MEK1/2 inhibition led to vimentin dispersion. Our work therefore elucidates the signaling axis SopB-Cdc42-MEK1/2 as mobilizing host vimentin to maintain concrete SCVs and identifies a mechanism contributing to Salmonella replication. Importantly, Trametinib, a clinically-approved MEK1/2 inhibitor identified in the screen, displayed significant Anti-infection efficacy against Salmonella both in vitro and in vivo, and may provide a therapeutic option for treating drug-tolerant salmonellosis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12755
    99.87%, Cdc42 GTPase Inhibitor