An infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli
Chunhui Miao,
Mingyu Yu,
Geng Pei,
Zhenyi Ma,
Lisong Zhang,
Jianming Yang,
Junqiang Lv,
Zhi-Song Zhang,
Evan T. Keller,
Zhi Yao () and
Quan Wang ()
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Chunhui Miao: Tianjin Medical University
Mingyu Yu: Tianjin Medical University
Geng Pei: Tianjin Medical University
Zhenyi Ma: Tianjin Medical University
Lisong Zhang: Nankai University
Jianming Yang: Tianjin Medical University
Junqiang Lv: Tianjin Medical University
Zhi-Song Zhang: Nankai University
Evan T. Keller: University of Michigan
Zhi Yao: Tianjin Medical University
Quan Wang: Tianjin Medical University
Nature Communications, 2021, vol. 12, issue 1, 1-15
Abstract:
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.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22726-8
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DOI: 10.1038/s41467-021-22726-8
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