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.
Highlights
Host cells use several anti-bacterial pathways to defend against pathogens
To further examine this possibility, endogenous RhoB was knocked down using specific siRNAs, which led to a threefold increase of intracellular bacteria, compared with that achieved by siScr control (Fig. 1e)
The mechanism through which ATG16L1 deficiency decreases uropathogenic Escherichia coli (UPEC) infection is independent of autophagy but depends on superficial urothelial cell architectural alterations and enhanced IL-1β-mediated hyperinflammatory response in macrophages[10,11,12,13]
Summary
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. Lots of host factors responsible for sensing invasive pathogens and initiating anti-bacterial effects are induced during bacterial infections. It can be triggered through recognition of pathogenassociated molecular patterns (PAMPs) by a variety of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs)[15,16,17]. The present study reveals the role of RhoB in defending against intracellular UPEC and highlights the importance of the physical association between RhoB, Beclin 1, and Hsp[90] to achieve anti-bacterial effects
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