2. Academic Validation
  3. An infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli

An infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli

  • Nat Commun. 2021 May 10;12(1):2587. doi: 10.1038/s41467-021-22726-8.
Chunhui Miao  # 1,  Mingyu Yu  # 1,  Geng Pei 1,  Zhenyi Ma 2,  Lisong Zhang 3,  Jianming Yang 1,  Junqiang Lv 1,  Zhi-Song Zhang 3,  Evan T Keller 4,  Zhi Yao 5 6,  Quan Wang 7
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China.
  • 3 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
  • 4 Department of Urology, University of Michigan, Ann Arbor, MI, USA.
  • 5 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. yaozhi@tmu.edu.cn.
  • 6 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Tianjin, China. yaozhi@tmu.edu.cn.
  • 7 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. wangquan@tmu.edu.cn.
  • # Contributed equally.
PMID: 33972537 DOI: 10.1038/s41467-021-22726-8
Abstract

Host cells use several anti-bacterial pathways to defend against pathogens. Here, using a uropathogenic Escherichia coli (UPEC) Infection model, we demonstrate that Bacterial infection upregulates RhoB, which subsequently promotes intracellular bacteria clearance by inducing LC3 lipidation and autophagosome formation. RhoB binds with Beclin 1 through its residues at 118 to 140 and the Beclin 1 CCD domain, with RhoB Arg133 being the key binding residue. Binding of RhoB to Beclin 1 enhances the Hsp90-Beclin 1 interaction, preventing Beclin 1 degradation. RhoB also directly interacts with HSP90, maintaining RhoB levels. UPEC infections increase RhoB, Beclin 1 and LC3 levels in bladder epithelium in vivo, whereas Beclin 1 and LC3 levels as well as UPEC clearance are substantially reduced in RhoB+/- and RhoB-/- mice upon Infection. We conclude that when stimulated by UPEC infections, host cells promote UPEC clearance through the RhoB-Beclin 1-HSP90 complex, indicating RhoB may be a useful target when developing UPEC treatment strategies.

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