Role of Copper in Urinary Tract Infection. We have demonstrated that copper is mobilized to urine as a host response during clinical UTI in patients. A non-human primate model of UTI recapitulates urinary copper mobilization observed in human UTI. Our findings, taken together with reports of fulminant UTI in patients with Menkes disease (who cannot absorb dietary copper), highlight an important and novel biological role for copper in the protection against UTI. Our investigations are focused on defining the mechanism of copper-mediated protection against UPEC colonization, and to determine how copper is mobilized to urine during UTI caused by UPEC. Our findings are anticipated to break new ground to develop novel interventions against UTI.
Copper homeostasis in bacterial pathogens. We are actively pursuing the mechanisms utilized by various bacterial pathogens to maintain copper homeostasis. We are using both forward and reverse genetic methods, complemented by proteomics to elucidate how bacterial pathogens respond, adapt and survive under copper stress. Knowledge of these processes are critical to understand how host-derived copper in involved in limiting bacterial growth during infection and to develop strategies to augment the toxicity of endogenous copper to bacterial pathogens.
UTI as diabetic complication. People with diabetes are highly susceptible to UTI. In the United States alone, almost 1 in 10 people (29.1 million) were diabetic in 2012. We are developing advanced models to understand diabetes-induced changes in the urinary tract during health and disease. By using small molecules, we can now distinguish the effects of increased urinary glucose-fueled bacterial overgrowth from diabetes-induced changes in the urinary tract that increases susceptibility to UTI.
Genetic basis of susceptibility to UTI. Alarmingly little is known about the influence of host genetics on susceptibility to UTI. We are investigating the role of genetic factors that contribute to UTI development or protection from UTI in a unique set of mouse strains. We have identified mouse strains that exhibit higher levels of resistance or susceptibility to bacterial UTI. Further characterization of these mouse strains is expected to shed light on the role host factors that determine the risk for UTI.
