The transcriptome of Escherichia coli Strain Nissle 1917 and EcN C6

As about one third of urate is excreted by small intestine and cleared by intestinal microorganisms, modulating gut microbiota could be an alternative approach for hyperuricemia. In this study, we engineered a probiotic E. coli Nissle 1917 (EcN) strain named EcN C6 to degrade urate by inserting a FtsP-uricase cassette into an “insulated site” located between the uspG and ahpF genes. Oral administration of EcN C6 successfully alleviated hyperuricemia and related symptoms in a purine-rich food-induced hyperuricemia rat model as well as an uox-knockout mouse model.

Most importantly, expression of FtsP-uricase in this insulated site did not influence the probiotic property or global gene transcription of EcN and restored the gut microbiota disturbed by hyperuricemia in vivo, suggesting EcN C6 is a safe and effective therapeutic candidate for hyperuricemia treatment. These results support further clinical development of EcN C6 for hyperuricemia disorders. Overall design: To characterize the transcriptional profile of EcN and EcN C6, triplicate cultures of each strain were incubated overnight in LB broth at 37℃, named WT-1, WT-2, WT-3, C6-1, C6-2, C6-3.