Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively investigated. In the present study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal Ca2+-related ion channel activities, resulting in chronic inflammation of the kidney along with rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in Ca2+-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign body infection. After the bladder was infected for 7 days, the data demonstrated that stones were presented and induced severe renal tubular breakage as well as altered levels of monocyte chemoattractant protein-1, cyclooxygenase-2, osteopontin, and transient receptor potential vanilloid member 5 expression, reflecting responses of kidney ion channels. Monocyte chemoattractant protein-1, osteopontin, and transient receptor potential vanilloid member 5 expression was significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, whereas cyclooxygenase-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal Ca2+-related ion channels and might support specific and targeted Ca2+-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.
Ion channels and bacterial infection: the case of β-barrel pore-forming protein toxins ofStaphylococcus aureus