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PMID: 33972537 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature communications ·Vol. 12 ·No. 1 ·2021-00-10 ·Pages 2587

Miao C, Yu M, Pei G, Ma Z, Zhang L, Yang J, Lv J, Zhang ZS, Keller ET, Yao Z, Wang Q

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.

MeSH Terms
Animals Autophagosomes/genetics,metabolism,ultrastructure Beclin-1/genetics,metabolism Cell Line Epithelium/metabolism,microbiology Escherichia coli Infections/genetics,metabolism,microbiology Female Gene Knockdown Techniques HSP90 Heat-Shock Proteins/genetics,metabolism Humans Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Electron, Transmission Microtubule-Associated Proteins/metabolism Protein Binding Protein Stability RNA, Small Interfering Recombinant Proteins Urinary Bladder/metabolism,microbiology Urinary Tract Infections/genetics,metabolism,microbiology Uropathogenic Escherichia coli/growth & development,pathogenicity rhoB GTP-Binding Protein/genetics,metabolism
Chemicals
Beclin-1 HSP90 Heat-Shock Proteins MAP1LC3A protein, human Microtubule-Associated Proteins RNA, Small Interfering Recombinant Proteins rhoB GTP-Binding Protein
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Miao Chunhui ORCID
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.
Yu Mingyu
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.
Pei Geng
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.
Ma Zhenyi ORCID
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China.
Zhang Lisong
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.
Yang Jianming
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.
Lv Junqiang
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.
Zhang Zhi-Song ORCID
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.
Keller Evan T
Department of Urology, University of Michigan, Ann Arbor, MI, USA.
Yao Zhi ORCID
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. | 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Tianjin, China. yaozhi@tmu.edu.cn.
Wang Quan ORCID
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.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/s41467-021-22726-8
Email
yaozhi@tmu.edu.cn
wangquan@tmu.edu.cn
Published
2021-00-10
Epub
2021-00-10
Pages
2587
Language
English
Region
England
NLM ID
101528555
PMCID
PMC8110956
Subset
IM
External Links
PubMed source DOI: 10.1038/s41467-021-22726-8 PMC Full Text View journal details
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