Abstract
Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XBT, a uric acid-degrading bacterium, from black-headed gull (Chroicocephalus ridibundus) feces. Using a polyphasic taxonomic approach, strain 44XBT was identified as a novel genus within the family Bacillaceae; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XBT had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (pucL, pucM, uraD, and allB) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%-99.70% amino acid identity. In vivo experiments revealed that 44XBT reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT. Importance: The increasing disease burden of hyperuricemia highlights the need for new therapeutic drugs and treatment strategies. Our study describes the developmental and application values of natural uric acid-degrading bacteria found in the gut of birds and broadened the source of bacteria with potential therapeutic value. Furthermore, the special physiology characteristics and genomic features of strain 44XBT are valuable for further study.