Evaluation of Biofilm-Induced Urinary Infection Stone Formation in a Novel Laboratory Model System

PURPOSE: Infection stones comprise approximately 15% of all urinary tract stones and are induced by infection with urease-positive pathogens. The bacteria within the stone matrix present significant treatment impediments compared to metabolic kidney stones. While much is known about how urinary composition regulates metabolic stone formation, there is a general lack of knowledge around which urinary factors regulate the rate of infection stone formation. Unfortunately, more in-depth research into infection stones is limited by the lack of suitable models for the real-time study of bacterial biofilm formation and stone formation under varying conditions. MATERIALS AND METHODS: We developed an in vitro model to study infection stone formation that closely represents the processes that occur in vivo, including the observed migration of ureolytic bacteria (oure culture of Proteus mirabilis) from the bladder to the kidneys, followed by biofilm and stone formation in the kidney. We used scanning electron and confocal laser microscopy, X-ray diffraction, biological counts, and dissolved chemical analyses to evaluate the model system. RESULTS: Crystals formed in the system resembled clinically-removed struvite stones in structure and composition. Results show that the degree of ureolysis required to significantly change urine pH is minimal, bacterial communities inhabit the ureter, and upstream colonization and struvite formation require a lag-time. CONCLUSIONS: These results have implications for the detection and treatment of struvite stones. Current studies using this model study specific urinary factors that regulate struvite formation to identify treatment options that combined with antibiotics improve the treatment of these stones and decrease recurrence.