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.

宿主细胞使用几种抗菌途径来防御病原体。在这里，使用尿路致病性大肠杆菌(UPEC) 感染模型，我们证明细菌感染上调 RhoB，其随后通过诱导 LC3 脂化和自噬体形成来促进细胞内细菌清除。RhoB 通过其 118 至 140 处的残基和 Beclin 1 CCD 结构域与 Beclin 1 结合，其中 RhoB Arg133 是关键的结合残基。RhoB 与 Beclin 1 的结合增强了 Hsp90-Beclin 1 的相互作用，防止了 Beclin 1 的降解。RhoB 还直接与 Hsp90 相互作用，维持 RhoB 水平。UPEC感染增加RhoB的，自噬基因Beclin 1和LC3水平在膀胱上皮体内，而自噬基因Beclin 1和LC3水平以及间隙UPEC在基本上减少RhoB的^+/-和RhoB ^-/-小鼠感染后。我们得出结论，当受到 UPEC 感染的刺激时，宿主细胞通过 RhoB-Beclin 1-HSP90 复合物促进 UPEC 清除，这表明 RhoB 在开发 UPEC 治疗策略时可能是一个有用的目标。