Breeding of Highly Efficient Uric Acid-Lowering Lactic Acid Bacteria by ARTP Mutation and its Transcriptomic Analysis

Area of Science:

• Microbiology
• Metabolic Disorders
• Biotechnology

Background:

• Hyperuricemia (HUA) is a widespread metabolic condition requiring effective uric acid-lowering therapies.
• Lactiplantibacillus plantarum Ta6, sourced from Xinjiang fermented foods, is a potential probiotic candidate.

Purpose of the Study:

• To develop and characterize a genetically stable mutant strain of L. plantarum Ta6 with enhanced uric acid-lowering capabilities.
• To investigate the molecular mechanisms underlying the improved efficacy of the mutant strain.

Main Methods:

• Atmospheric pressure room temperature plasma (ARTP) mutagenesis was used to generate mutant strain A2 from L. plantarum Ta6.
• Phenotypic assays assessed uric acid degradation, inosine and guanosine degradation, and in vitro xanthine oxidase (XOD) inhibition.
• Transcriptomic analysis (RNA-Seq) was performed to identify differentially expressed genes (DEGs).

Main Results:

• Mutant strain A2 exhibited a 16.29% increase in uric acid degradation and complete degradation of inosine and guanosine.
• Strain A2 showed a high XOD inhibition rate (86.89%), comparable to allopurinol.
• Transcriptomic data revealed alterations in purine metabolism pathways (e.g., upregulation of PRPS and HGPRT) and active cell wall remodeling (peptidoglycan biosynthesis).

Conclusions:

• Lactiplantibacillus plantarum A2 is a promising probiotic with significantly enhanced uric acid-lowering properties.
• ARTP mutagenesis effectively improved the strain's efficacy by modulating purine metabolism and cell wall structure.
• This study provides insights into the molecular basis of probiotic-mediated hyperuricemia management.