Insulated expression of periplasmic uricase inE. coliNissle 1917 for the treatment of hyperuricemia

Abstract

Hyperuricemia is a prevalent disease worldwide that is characterized by elevated urate levels in the blood owing to purine metabolic disorders, which can result in gout and comorbidities. As approximately one-third of urate is excreted by the small intestine and cleared by intestinal microorganisms, modulating the gut microbiota could be an attractive approach for hyperuricemia and gout treatment. In this study, we engineered a probiotic E. coli Nissle 1917 (EcN) strain, EcN C6, which expresses periplasmic uricase at an “insulated site”, for urate degeneration. Oral administration of EcN C6 successfully alleviated hyperuricemia, related symptom and gut microbiota in a purine-rich food-induced hyperuricemia rat model and a uox-knockout mouse model. Importantly, the expression of periplasmic uricase in the insulated site did not influence the probiotic properties or global gene transcription of EcN, suggesting that EcN C6 is a safe, effective and low cost therapeutic candidate for hyperuricemia treatment.