Oral gavage of <i>Lactococcus lactis</i> expressing urate oxidase regulates serum uric acid level in mice.

Hao CHENG; Guoqing XIONG; Jiazhen CUI; Zhili CHEN; Chen ZHU; Na SONG; Qingyang WANG; Xianghua XIONG; Gang LIU; Huipeng CHEN

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Oral gavage of Lactococcus lactis expressing urate oxidase regulates serum uric acid level in mice.

Author: Hao CHENG ¹ ; Guoqing XIONG ² ; Jiazhen CUI ¹ ; Zhili CHEN ¹ ; Chen ZHU ¹ ; Na SONG ³ ; Qingyang WANG ¹ ; Xianghua XIONG ¹ ; Gang LIU ¹ ; Huipeng CHEN ¹
Author Information

1. Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100071, China.
2. Institutes of Physical Science and Information Technology, Anhui University, Hefei 230039, Anhui, China.
3. Department of Critical Care Medicine, People's Hospital of Laoling, Laoling 253600, Shandong, China.
Publication Type:Journal Article
Keywords: Lactococcus lactis; hyperuricemia; hyperuricemia model mouse; safety; urate oxidase
MeSH: Animals; Lactococcus lactis/metabolism*; Urate Oxidase/genetics*; Mice; Uric Acid/blood*; Hyperuricemia; Humans; Administration, Oral; Aspergillus flavus/genetics*; Male
From: Chinese Journal of Biotechnology 2024;40(11):4111-4119
CountryChina
Language:Chinese
Abstract: Urate oxidase (Uox) plays a pivotal role in uric acid (UA) degradation, and it has been applied in controlling serum UA level in clinical treatment of hyperuricemia (HUA). However, because Uox is a heterogenous protein to the human body, the immune rejections typically occur after intravenous administration, which greatly hampers the application of Uox-based agents. In this study, we used Lactococcus lactis NZ9000, a food-grade bacterium, as a host to express exogenous Uox genes, to generate the Uox-expressing engineered strains to treat HUA. Aspergillus flavus-derived Uox (aUox) and the "resurrected" human-derived Uox (hUox) were cloned into vector and expressed in NZ9000, to generate engineered strains, respectively. The engineered NZ9000 strains were confirmed to express Uox and showed UA-lowering activity in a time-dependent manner in vitro. Next, in an HUA mice model established by oral gavage of yeast paste, the UA levels were increased by 85.4% and 106.2% at day 7 and day 14. By contrast, in mice fed with NZ9000-aUox, the UA levels were increased by 39.5% and 48.3% while in mice fed with NZ9000-hUox were increased by 57.0% and 82.9%, suggesting a UA-lowering activity of both engineered strains. Furthermore, compared with allopurinol, the first-line agent for HUA treatment, mice fed with NZ9000-aUox exhibited comparable liver safety but better kidney safety than allopurinol, indicating that the use of engineered NZ9000 strains not only alleviated kidney injury caused by HUA, but could also avoided the risk of kidney injury elicited by using allopurinol. Collectively, our study offers an effective and safe therapeutic approach for HUA long-term treatment and controlling.