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

• Published in: Nature communications 2021-05, Vol.12 (1), p.2587-2587, Article 2587
• Main Authors: Miao, Chunhui, Yu, Mingyu, Pei, Geng, Ma, Zhenyi, Zhang, Lisong, Yang, Jianming, Lv, Junqiang, Zhang, Zhi-Song, Keller, Evan T., Yao, Zhi, Wang, Quan
• Format: Article
• Language: English
• Subjects: 13; 13/109; 13/89; 14/19; 631/250/2499; 631/326/421; 692/4025/2768/1865; 82/1; Animals; Antiinfectives and antibacterials; Autophagosomes - genetics; Autophagosomes - metabolism; Autophagosomes - ultrastructure; Bacteria; Bacterial diseases; Bacterial infections; Beclin-1 - genetics; Beclin-1 - metabolism; Binding; Biodegradation; Bladder; Cell Line; Clearances; E coli; Epithelium; Epithelium - metabolism; Epithelium - microbiology; Escherichia coli; Escherichia coli Infections - genetics; Escherichia coli Infections - metabolism; Escherichia coli Infections - microbiology; Female; Gene Knockdown Techniques; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humanities and Social Sciences; Humans; Infections; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - metabolism; multidisciplinary; Protein Binding; Protein Stability; Recombinant Proteins; Residues; rhoB GTP-Binding Protein - genetics; rhoB GTP-Binding Protein - metabolism; RNA, Small Interfering; Science; Science (multidisciplinary); Urinary Bladder - metabolism; Urinary Bladder - microbiology; Urinary Tract Infections - genetics; Urinary Tract Infections - metabolism; Urinary Tract Infections - microbiology; Uropathogenic Escherichia coli - growth & development; Uropathogenic Escherichia coli - pathogenicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22726-8

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. Bacterial invasion can lead to multiple host cell responses. Here, the authors show that in a model of uropathogenic E. coli, RhoB is upregulated and induces autophagosome formation in a complex with Beclin1 and Hsp90, promoting bacterial clearance.