School of Biomedical Sciences, UNSW Sydney, Sydney, NSW 2052, Australia.
St George Hospital, UNSW Sydney, Kogarah, NSW 2217, Australia.
Pathog Dis. 2024 Feb 7;82. doi: 10.1093/femspd/ftae026.
Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), have an unclear impact on bladder mucosal physiology. This study investigates UPEC's effects on the urothelium and lamina propria using an ex vivo porcine bladder model. Bladder mucosal strips were analysed for contractile responses to acetylcholine, serotonin, and neurokinin A. Given rising antibiotic resistance, non-antibiotic agents such as cranberry and d-mannose were also evaluated for their potential to prevent UPEC-induced damage. The findings of the current study revealed that UPEC significantly compromised urothelial integrity, barrier function, and permeability, with loss of urothelial cells, uroplakins, and tight junction protein ZO-1 expression. Additionally, infected bladders exhibited a markedly enhanced contractile response to serotonin compared to uninfected controls. Notably, neither cranberry nor d-mannose offered protection against UPEC-mediated damage or mitigated the heightened serotonin-induced contractility. This study provides novel insights into how UPEC disrupts bladder cell biology and highlights the possible involvement of serotonin in the pathophysiology of UTIs.
尿路感染（UTIs）主要由尿路致病性大肠杆菌（UPEC）引起，其对膀胱黏膜生理学的影响尚不清楚。本研究使用猪离体膀胱模型探讨了 UPEC 对尿路上皮和固有层的影响。分析了膀胱黏膜条对乙酰胆碱、血清素和神经激肽 A 的收缩反应。鉴于抗生素耐药性不断上升，目前还评估了蔓越莓和 D-甘露糖等非抗生素药物预防 UPEC 诱导损伤的潜力。本研究结果表明，UPEC 显著损害了尿路上皮的完整性、屏障功能和通透性，导致尿路上皮细胞、尿路上皮蛋白和紧密连接蛋白 ZO-1 的表达丢失。此外，与未感染对照组相比，感染的膀胱对血清素的收缩反应明显增强。值得注意的是，蔓越莓和 D-甘露糖均不能预防 UPEC 介导的损伤，也不能减轻血清素诱导的收缩性增强。本研究提供了 UPEC 如何破坏膀胱细胞生物学的新见解，并强调了血清素可能参与 UTIs 的病理生理学。
