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

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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.