Browsing by Author "Hobbs, Trace"

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Evaluation of Biofilm Induced Urinary Infection Stone Formation in a Novel Laboratory Model System
(2018-01) Hobbs, Trace; Schultz, Logan N.; Lauchnor, Ellen G.; Gerlach, Robin; Lange, D.
Purpose Infection stones, which comprise approximately 15% of all urinary tract stones, are induced by infection with urease-positive pathogens. The bacteria in 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 of 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 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. The model closely represents the processes that occur in vivo, including the observed migration of ureolytic bacteria (our 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 that formed in the system resembled clinically removed struvite stones in structure and composition. Results showed that the degree of ureolysis required to significantly change urine pH was minimal, bacterial communities inhabited the ureter, and upstream colonization and struvite formation required lag time. Conclusions These results have implications for the detection and treatment of struvite stones. Currently this model is being used to study specific urinary factors that regulate struvite formation to identify treatment options, which combined with antibiotics would improve treatment of these stones and decrease recurrence.
Struvite stone formation by ureolytic biofilm infections
(2016) Schultz, Logan N.; Connolly, James M.; Lauchnor, Ellen G.; Hobbs, Trace; Gerlach, Robin
This chapter describes how urinary tract infections can lead to stone formation. The most frequent type of infection stone is struvite (MgNH4PO4â€‰Â·â€‰6H2O), although it is common that struvite stones and infections are associated with other stone types, often forming large staghorn calculi. A complete understanding of struvite stone formation requires knowledge of the pathogen biology, including metabolic activity and motility, as well as a basic understanding of how minerals form.The pathogens responsible for struvite stones are those that break down urea into ammonium (NH4 +) and inorganic carbon. This reaction, known as ureolysis, increases the pH of urine and the concentration of NH4 +, thus increasing the saturation index of struvite. If supersaturation is reached, i.e. the ion activity product (IAP) is greater than the ion activity product at equilibrium (Ksp), struvite stone formation is possible.An important consideration with urinary tract infections is that pathogens often form attached communities, known as biofilms, which help them to survive physical and chemical stresses. Not only are biofilm-related infections more difficult to treat, but they can facilitate stone formation by creating gradients in chemical concentrations near surfaces. Modern laboratory bioreactors and computer models, described in this chapter, are improving our understanding of how and why infection stones such as struvite form. Current treatment options for infection stones can be painful or ineffective. As more is learned about the complex microbe-fluid-mineral interactions, less-invasive treatments and more-effective prevention strategies will be developed.Book title: The Role of Bacteria in Urology Lange D, Chew B, (Eds.): Springer, 2015; pp. 41â€“49.