Center for Biofilm Engineering

Thesis Abstract:  

"Molecular aspects of uranium toxicity: Speciation and physiological targeting" 

Uranium (U), as the uranyl ion (UO₂²⁺) is a widely distributed contaminant at several Department of Energy (DOE) sites, former war zones, and across the globe. Although many U remediation efforts depend on U-bacterial interactions, little information regarding U-bacterial interactions resolved at the molecular level exist. In this study, experiments were performed aimed at understanding the effect of molecular UO₂²⁺ speciation on bacterial bioaccumulation and toxicity using an environmental Pseudomonas sp. isolate. Results showed that the charge and stability of UO₂²⁺ species largely controlled the extent of UO₂²⁺ bioaccumulation and UO₂²⁺ toxicity, respectively.  Further experimentation, including a combination of in vivo, in vitro, and in silico studies, revealed a specific mechanism of UO₂²⁺ toxicity, the first to be reported. This mechanism involves the binding of UO₂²⁺ to pyrroloquinoline quinone (PQQ), a cofactor present in a number of bacterial dehydrogenase enzymes. Based on the specific binding mode of UO₂²⁺ to PQQ, it was hypothesized that the present work has direct implications for UO₂²⁺ inhibition of flavoproteins, potentially extending the application of the findings of this work to eukaryotic systems. Recent trends suggest that U-related activity will increase in the near future, and therefore understanding fundamental interactions between UO₂²⁺ and living systems is both an environmental and human health imperative.
 

Molecular aspects of uranium toxicity: Speciation and physiological targeting, Thesis Defense by Michael VanEngelen, PhD Candidate in Chemical and Biological Engineering Montana State University, August 2009