Abstract：
Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transport to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular PI3P levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling pre-autophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute UTI.
摘要：
尿路感染主要由泌尿致病性大肠杆菌(UPEC)引起。UPEC通过梭形囊泡感染膀胱上皮细胞（BECs），并通过使用外膜磷脂酶PldA破坏梭形囊泡膜而逃逸到细胞质中，并建立生物膜样细胞内细菌群落（IBC）以防止宿主免疫清除。胞质UPEC被自噬捕获形成自噬体，然后运输到溶酶体，引发溶酶体的自发胞吐。UPEC逃避自噬识别和形成IBC的机制尚不清楚。这里,我们证明通过抑制自噬通量，UPECPldA降低BECs的溶酶体胞吐作用。通过降低细胞内PI3P水平，UPECPldA增加NDP52颗粒的积累并减少NDP52对自噬的靶向，因此停止前自噬体结构。因此，我们的结果揭示了PldA抑制自噬通量的关键作用，有利于UPEC逃避溶酶体胞吐，从而导致急性UTI。
