Theses and Dissertations at Montana State University (MSU)
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Item Omics approaches identify molecular mechanisms of arsenic-microbial interactions(Montana State University - Bozeman, College of Letters & Science, 2019) Rawle, Rachel Anna; Chairperson, Graduate Committee: Timothy R. McDermott and Brian Bothner (co-chair); Yoon-Suk Kang, Brian Bothner, Gejiao Wang and Timothy R. McDermott were co-authors of the article, 'Transcriptomics analysis defines global cellular response of Agrobacterium tumefaciens 5A to arsenite exposure regulated through the histidine kinases phor and aios' in the journal 'Environmental microbiology' which is contained within this dissertation.; Monika Tokmina-Lukaszewska, Zunji Shi, Brian Tripet, Fang Dang, Timothy R. McDermott, Valerie Copie, Gejiao Wang and Brian Bothner were co-authors of the article, 'Metabolic responses to arsenite exposure regulated through histidine kinases phor and aios in Agrobacterium tumefaciens 5A' submitted to the journal 'Environmental microbiology' which is contained within this dissertation.Arsenic is a class I carcinogen and causes various cancers and diseases. Its toxicity, prevalence, and potential for human exposure has classified arsenic as the number one environmental toxin according to the Environmental Protection Agency. Contamination of groundwater and soil leads to over 200 million human exposures above the health limit. In every environment where arsenic and microbes coexist, microbes are the principal drivers of arsenic speciation, which is directly related to bioavailability, toxicity, and bioaccumulation. These speciation events drive arsenic behavior in the soil, water, and as recent data suggests, human-associated microbiomes. This dissertation details arsenic-microbial interactions through an omics platform, utilizing transcriptomics, metabolomics, and proteomics profiling as a way to globally assess the impacts of arsenic exposure. This work followed two main aims: (1) characterize cell metabolism during arsenic exposure in soil bacterium Agrobacterium tumefaciens 5A, a model organism for arsenite oxidation, and (2) assess the impacts of specific arsenic-processing bacteria within the gut microbiome of mammals. The results of this work provide a foundational understanding for how arsenic speciation events are regulated and how they affect nutrient cycling in environmental systems, which is necessary for bioremediation and health initiatives.Item Investigating arsenic-microbiome interactions in the gut using murine models(Montana State University - Bozeman, College of Letters & Science, 2019) Coryell, Michael Philip; Chairperson, Graduate Committee: Seth Walk; B. A. Roggenbeck and Seth T. Walk were co-authors of the article, 'The human gut microbiome's influence on arsenic toxicity' submitted to the journal 'Current pharmacology reports' which is contained within this thesis.; M. McAlpine, N.V. Pinkham, T.R. McDermott and Seth T. Walk were co-authors of the article, 'The gut microbiome is required for full protection against acute arsenic toxicity in mouse models' in the journal 'Nature communications' which is contained within this thesis.; M. Yoshinaga, T.R. McDermott and Seth T. Walk were co-authors of the article, 'Speciation of excreted arsenicals from germ free and conventional AS3MT knockout mice exposed to inorganic arsenate' which is contained within this thesis.Drinking water contamination with arsenic is a wide-spread public health concern, potentially affecting over 140 million people across at least 40 different countries. Current understanding of biological and behavioral factors influencing clinical outcomes is insufficient to explain the variation observed in arsenic-related disease prevalence and severity. The intestinal microbiome in humans is a dynamic and active ecosystem with demonstrated potential to mediate arsenic metabolism in vitro and distinct variability between individuals. This dissertation investigates arsenic-microbiome interactions, with a focus on determining how microbiome activity influences host-response and toxicity from arsenic exposures. Chapter 2 overviews common exposure routes, important metabolic pathways, and current evidence of arsenic-microbiome interactions in humans or experimental animal models. Chapter 3, the initial approach was to experimentally perturb the microbiome of common laboratory mice during arsenic exposure, measuring arsenic excretion in the stool and accumulation in host tissues. Arsenic sensitive gene-knockout mice were used to determine the microbiome's influence on subacute arsenic-induced mortality. Disrupting microbiome function--first by antibiotic treatment, then by deriving mice germ free--dramatically reduced survival times during severe arsenic exposures. Transplantation of human fecal communities into germ free mice effectively complemented the loss of function from microbiome disruption in these mice. Chapter 4 examines microbiome's impact on arsenic metabolism in germ free and conventional mice from this same arsenic-sensitive genetic background. These mice are deficient for the primary metabolic pathway involved in arsenic detoxification in both humans and mice, facilitating a more complete experimental isolation of microbiome and host metabolisms. This study provides evidence of microbiome-dependent changes in the elimination routes and metabolic transformation of ingested arsenic and provides a new experimental model for studying arsenic metabolism in the gut.Item Copper injury of Escherichia coli(Montana State University - Bozeman, College of Agriculture, 1984) Domek, Matthew Joseph