No abstract

Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli, then gel electrophoresis and nanoLC-MS/MS to detect the crystal-adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK-2 cell in vitro. By transurethral injection of wild-type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK-2 cell oxidative injury and activated the inflammation-related NF-κB/P38 signaling pathway. Wild-type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation-related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF-κB/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment.

Escherichia coli (E. coli) strains cause the majority of urinary tract infections (UTIs) and are resistant to various antibiotics. Therefore, it is imperative to explore novel host-target therapies. As a...