RNA interference-mediated hookworm control by gut-dwelling lactic acid bacteria.

Background: The complex life cycle of geohelminth parasites make it difficult to manage repeated infections that occur in endemic areas, that requires the development of new therapeutic strategies. Human hookworm Aims and Objectives: In this study, we attempted to develop a new type of therapy using value-added probiotics-producing antiparasitic RNA interference (RNAi) molecules against a vital hookworm ( Results: The engineered probiotics colonizing the gut, when consumed by the parasite released the dsRNA that which knocked down the target by RNAi interfering with their moulting and tissue migration. The initial penetration of the larvae into the gut lining was reduced by 70%, followed by a reduction of up to 50% in migration to the critical organs. The damage caused to the liver (30%-40%) and the kidneys (50%-60%) by the hookworm in mouse models as quantitated by enzymes released in the blood was totally reversed when the worms were pre fed with the engineered L. lactis before the parasite challenge. Conclusions: We believe that this is the first demonstrated knockdown of a target gene in hookworms using probiotics genetically engineered to stimulate RNAi (RNAi food), administered through the oral route. This novel method of parasite control when extended to other hookworms,