Chenming Zhao1, Huan Yang1, Xiaojing Zhu2, Yang Li2, Ning Wang1, Shanfu Han1, Hua Xu3, Zhiqiang Chen1, Zhangqun Ye1. 1. Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. 2. College of Life Science, Hubei University, Wuhan, China. 3. Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xuhua@hust.edu.cn.
Abstract
OBJECTIVE: To develop recombinant lactic acid bacteria (LAB) strains that express oxalate-degrading enzymes through biotechnology-based approach for the treatment of hyperoxaluria by oral administration. MATERIAL AND METHODS: The coding gene of oxalate decarboxylase (ODC) and oxalate oxidase (OxO) was transformed into Lactococcus lactis MG1363. The oxalate degradation ability in vitro was evaluated in media with high concentration of oxalate. Hyperoxaluria rat models through high oxalate diet were given recombinant LAB through oral administration. Twenty-four-hour urinary oxalate was measured, and kidney stone formation was investigated. RESULTS: LAB recombined with the coding gene of ODC could effectively decrease the amount of oxalate in the media and in the urine of rats. Moreover, the formation of calcium oxalate crystals in kidneys was also inhibited. The acid-induced promoter p170 significantly enhanced the reduction of hyperoxaluria. However, recombinant LAB expressing heterologous OxO showed less efficiency in oxalate degradation even in the presence of p170. CONCLUSION: LAB expressing ODC is more efficient in degradation of oxalate in vitro and in vivo than that expressing OxO. This present study provided novel recombinant probiotic strains as a potential treatment tool against oxalosis.
OBJECTIVE: To develop recombinant lactic acid bacteria (LAB) strains that express oxalate-degrading enzymes through biotechnology-based approach for the treatment of hyperoxaluria by oral administration. MATERIAL AND METHODS: The coding gene of oxalate decarboxylase (ODC) and oxalate oxidase (OxO) was transformed into Lactococcus lactis MG1363. The oxalate degradation ability in vitro was evaluated in media with high concentration of oxalate. Hyperoxaluriarat models through high oxalate diet were given recombinant LAB through oral administration. Twenty-four-hour urinary oxalate was measured, and kidney stone formation was investigated. RESULTS: LAB recombined with the coding gene of ODC could effectively decrease the amount of oxalate in the media and in the urine of rats. Moreover, the formation of calcium oxalate crystals in kidneys was also inhibited. The acid-induced promoter p170 significantly enhanced the reduction of hyperoxaluria. However, recombinant LAB expressing heterologous OxO showed less efficiency in oxalate degradation even in the presence of p170. CONCLUSION: LAB expressing ODC is more efficient in degradation of oxalate in vitro and in vivo than that expressing OxO. This present study provided novel recombinant probiotic strains as a potential treatment tool against oxalosis.
Authors: Matthew R D'Costa; Annamaria T Kausz; Kevin J Carroll; Jóhann P Ingimarsson; Felicity T Enders; Kristin C Mara; Ramila A Mehta; John C Lieske Journal: Nephrol Dial Transplant Date: 2021-12-02 Impact factor: 5.992