Université Clermont Auvergne, INRAE, MEDiS, F-63000 Clermont-Ferrand, France.
GSK, Siena, Italy.
Emerg Microbes Infect. 2020 Dec;9(1):1065-1076. doi: 10.1080/22221751.2020.1768804.
Enterohaemorrhagic (EHEC) are bacterial pathogens responsible for life-threatening diseases in humans such as bloody diarrhoea and the hemolytic and uremic syndrome. To date, no specific therapy is available and treatments remain essentially symptomatic. In recent years, we demonstrated that nitric oxide (NO), a major mediator of the intestinal immune response, strongly represses the synthesis of the two cardinal virulence factors in EHEC, namely Shiga toxins (Stx) and the type III secretion system, suggesting NO has a great potential to protect against EHEC infection. In this study, we investigated the interplay between NO and EHEC using mouse models of infection. Using a NO-sensing reporter strain, we determined that EHEC sense NO in the gut of infected mice. Treatment of infected mice with a specific NOS inhibitor increased EHEC adhesion to the colonic mucosa but unexpectedly decreased Stx activity in the gastrointestinal tract, protecting mice from renal failure. Taken together, our data indicate that NO can have both beneficial and detrimental consequences on the outcome of an EHEC infection, and underline the importance of studies to increase our knowledge in host-pathogen interactions.
产志贺毒素（Shiga） （EHEC） 是一种能引起人类生命威胁性疾病的细菌病原体，如血便和溶血尿毒综合征。迄今为止，尚无特定的治疗方法，治疗仍然主要是对症治疗。近年来，我们证明了一氧化氮（NO），一种肠道免疫反应的主要介质，强烈抑制 EHEC 中两种主要毒力因子，即志贺毒素（Stx）和 III 型分泌系统的合成，这表明一氧化氮具有很大的潜力来预防 EHEC 感染。在这项研究中，我们使用感染的小鼠模型研究了 NO 与 EHEC 之间的相互作用。使用一氧化氮感应报告菌株，我们确定 EHEC 在感染小鼠的肠道中感知 NO。用特定的 NOS 抑制剂治疗感染的小鼠会增加 EHEC 对结肠黏膜的黏附，但出人意料的是，它会降低胃肠道中的 Stx 活性，从而保护小鼠免受肾衰竭。总之，我们的数据表明，NO 对 EHEC 感染的结果可能既有有益的影响，也有有害的影响，并强调了进行研究以增加我们对宿主-病原体相互作用的了解的重要性。
