Escherichia coli strain Nissle has been used as a probiotic and therapeutic agent for over a century. Reports suggest that Nissle protects mice from enterohemorrhagic E. coli (EHEC) O157:H7 strains; however, mice are not very susceptible to O157:H7 and are not accurate models for O157:H7 infection in humans. Also, Nissle is closely related to uropathogenic E. coli (UPEC) strain CFT073, suggesting that Nissle could have pathogenic potential. To assess the safety of and protection conferred by Nissle, we modeled infection in stem cell-derived human intestinal organoids (HIOs). HIOs replicate the structure and function of human intestinal tissue. HIOs have a lumen enclosed by a single cell layer of differentiated epithelium, which is surrounded by a diffuse mesenchymal layer. An epithelial barrier which excludes the luminal contents from the surrounding cell layers and medium develops. Nissle appeared to be nonpathogenic; 10³ CFU were microinjected into the lumen, and after 3 days, 10⁷ CFU were recovered and the epithelial barrier remained intact. In contrast, microinjected EHEC and UPEC bacteria destroyed the epithelial barrier. To assess the protection conferred by Nissle, HIOs microinjected with Nissle were challenged after 18 to 24 h with EHEC or UPEC. Preincubation with Nissle prevented the loss of the epithelial barrier function, the loss of E-cadherin expression, the increased production of reactive oxygen species, and apoptosis. Nissle did not replicate in the HIO coculture, while the pathogenic strains did replicate, suggesting that Nissle conferred protection via activation of host defenses and not by eliminating competing strains. Nissle was shown to be susceptible to some Shiga toxin phage, and Nissle lysogens could produce Shiga toxin.

中文翻译：

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人类肠道类器官中大肠杆菌尼塞尔的益生菌特性。

一个多世纪以来，大肠杆菌Nissle 菌株一直被用作益生菌和治疗剂。报告表明 Nissle 可保护小鼠免受肠出血性大肠杆菌(EHEC) O157:H7 菌株的侵害；然而，小鼠对 O157:H7 不太敏感，也不是人类 O157:H7 感染的准确模型。此外，Nissle 与泌尿道致病性大肠杆菌(UPEC) 菌株 CFT073密切相关，表明 Nissle 可能具有致病潜力。为了评估 Nissle 的安全性和保护作用，我们对干细胞衍生的人类肠道类器官 (HIO) 的感染进行了建模。HIO 复制人类肠道组织的结构和功能。HIO 具有一个由分化上皮单细胞层包围的管腔，该管腔被弥漫性间质层包围。形成上皮屏障，将管腔内容物排除在周围细胞层和培养基之外。尼塞尔似乎不具有致病性；将10 ³ CFU显微注射到管腔中，3天后，10 ⁷ CFU恢复并且上皮屏障保持完整。相比之下，显微注射的 EHEC 和 UPEC 细菌破坏了上皮屏障。为了评估 Nissle 赋予的保护作用，显微注射 Nissle 的 HIO 在 18 至 24 小时后用 EHEC 或 UPEC 进行攻击。与 Nissle 预孵育可防止上皮屏障功能丧失、E-钙粘蛋白表达丧失、活性氧产生增加和细胞凋亡。Nissle 在 HIO 共培养物中不复制，而致病菌株确实复制，这表明 Nissle 通过激活宿主防御而不是消除竞争菌株来提供保护。尼塞尔被证明对某些志贺毒素噬菌体敏感，尼塞尔溶原菌可以产生志贺毒素。