Characterization of the mechanisms of action of nanobodies that interfere with the infection of chicken gut epithelial cells by Salmonella

人类致病细菌肠沙门氏菌通常存在于家禽的肠道中。食用受感染的鸡肉和鸡蛋及其衍生物是人类沙门氏菌感染暴发的主要和最重要的来源。 沙门氏菌病会引起腹泻、发烧和腹部痉挛。大多数人在没有治疗的情况下几天后就会恢复。然而，在某些情况下，严重腹泻和脱水的发生以及感染的全身性传播使沙门氏菌病成为一种威胁生命的疾病，需要住院治疗。老年人、婴儿和免疫系统受损的患者更容易感染这种严重的疾病，除非及时使用正确的抗生素进行治疗，否则有死亡的风险。目前还没有广泛有效的策略来干预沙门氏菌在肉鸡体内的定植，以防止人类感染沙门氏菌。 纳米抗体是自然界中已知的最小的抗体，由骆驼科(如骆驼、骆驼和羊驼)和鲨鱼产生。与传统抗体相比，最近发现的抗体具有免疫学和生物技术方面的优势。事实上，纳米抗体可以很容易地在细菌中表达，并以显著较低的成本大量生产。 我们的工业合作伙伴AbCelex开发了一个针对沙门氏菌的纳米体库。因此，这里提出的研究的目标将是在AbCelex的纳米体库中识别能够保护鸡肉免受沙门氏菌感染的抗体，并研究它们的作用机制。这些研究的结果将有助于了解选定的抗沙门氏菌纳米体的作用机理，并促进基于纳米体的技术的商业应用，以控制和检测食物链中的沙门氏菌。

The human pathogenic bacteria Salmonella enterica is commonly found in the intestine of poultry. Consumption of infected chicken and eggs, and its derivatives, is the main and most important source of Salmonella infection outbreaks in humans. Salmonellosis produces diarrhoea, fevers and abdominal cramps. Most people recover after few days without treatment. However, in some cases the occurrence of severe diarrhea and dehydration followed by systemic spreading of the infection turns Salmonellosis into a life-threatening disease that requires hospitalization. The elderly, infants, and patients with impaired immune systems are more susceptible to the severe form of this disease and in risk of death, unless treated promptly with the correct antibiotics. At present no widely effective strategy is available to interfere with Salmonella colonization of broiler chickens to prevent the infection in humans. Nanobodies, the smallest antibodies known in nature, are produced by members of the family Camelidae (like camels, llamas and alpacas) and sharks. This recently discovered antibodies present immunological and biotechnological advantages respect to the conventional antibodies. Indeed, nanobodies can be easily expressed in bacteria and produced in large quantities at a significantly lower cost.[11]. Our industrial partner, AbCelex developed a library of nanobodies, against Salmonella. Thus, the objective of the studies proposed here will be to identify in AbCelex's nanobodies library those antibodies that can protect chicken against Salmonella infection, and investigate their mechanisms of action. The outcome of these studies will help in understanding the mechanism of action selected anti- Salmonella nanobodies and to facilitate commercial implementation of nanobody-based technologies for controlling and detecting Salmonella in the food chain.