Cardiovascular disease associated with hyperphosphatemia is a leading cause of mortality in patients with chronic kidney disease(CKD).Although treatments such as dialysis,phosphorus-restricted diets,and phosphate bind...Cardiovascular disease associated with hyperphosphatemia is a leading cause of mortality in patients with chronic kidney disease(CKD).Although treatments such as dialysis,phosphorus-restricted diets,and phosphate binders are available,these therapies can reduce the quality of life for CKD patients and are associated with side effects.Probiotics,particularly those that accumulate polyphosphate,have emerged as a promising alternative without harmful side effects.This study aimed to enhance the polyphosphate-accumulating ability of Lactiplantibacillus paraplantarum KCCM 11826P using inverse metabolic engineering.Random mutagenesis was performed,and fluorescence-activated cell sorting(FACS)was used to select strains with enhanced phosphate accumulation capacity.After resequencing,we identified that the selected L.paraplantarum SNUP7 strain,derived from KCCM 11826P,exhibited mutations in the tuf,dnaK,and groL genes,and it absorbed 76.01% more phosphorus in a phosphate-rich medium compared to the wild-type strain.In a CKD rat model administered L.paraplantarum SNUP7 probiotics(Nx+P),blood phosphorus levels decreased by 30.5% relative to the vehicle group(Nx+V).Additionally,kidney injury was significantly suppressed by 53.1%in the Nx+P group,whereas no such effect was observed in the Nx+V group.These findings indicate that L.paraplantarum SNUP7 functions as a biophosphate binder with therapeutic potential for alleviating CKD symptoms,improving patients’quality of life.As a novel probiotic strain with enhanced phosphate-binding capacity,L.paraplantarum SNUP7 offers a promising therapeutic approach for CKD-related complications.展开更多
基金supported by a National Research Foundation of Korea grant from the Korean Government(Ministry of Science and ICTMSIT)(NRF-2021R1F1A1058927)the Technology Innovation Program(or Industrial Strategic Technology Development Program)(20018683,Development of technology for manufacturing biomass-based cellulose fibers and commercializing edible coating)funded By the Ministry of Trade,Industry and Energy(MOTIE,Korea).
文摘Cardiovascular disease associated with hyperphosphatemia is a leading cause of mortality in patients with chronic kidney disease(CKD).Although treatments such as dialysis,phosphorus-restricted diets,and phosphate binders are available,these therapies can reduce the quality of life for CKD patients and are associated with side effects.Probiotics,particularly those that accumulate polyphosphate,have emerged as a promising alternative without harmful side effects.This study aimed to enhance the polyphosphate-accumulating ability of Lactiplantibacillus paraplantarum KCCM 11826P using inverse metabolic engineering.Random mutagenesis was performed,and fluorescence-activated cell sorting(FACS)was used to select strains with enhanced phosphate accumulation capacity.After resequencing,we identified that the selected L.paraplantarum SNUP7 strain,derived from KCCM 11826P,exhibited mutations in the tuf,dnaK,and groL genes,and it absorbed 76.01% more phosphorus in a phosphate-rich medium compared to the wild-type strain.In a CKD rat model administered L.paraplantarum SNUP7 probiotics(Nx+P),blood phosphorus levels decreased by 30.5% relative to the vehicle group(Nx+V).Additionally,kidney injury was significantly suppressed by 53.1%in the Nx+P group,whereas no such effect was observed in the Nx+V group.These findings indicate that L.paraplantarum SNUP7 functions as a biophosphate binder with therapeutic potential for alleviating CKD symptoms,improving patients’quality of life.As a novel probiotic strain with enhanced phosphate-binding capacity,L.paraplantarum SNUP7 offers a promising therapeutic approach for CKD-related complications.
