Comparing the mechanisms of metal action in bacteria: insight into novel genes involved in silver, gallium and copper resistance and toxicity in Escherichia coli

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dc.contributor.advisorTurner, Raymond Joseph
dc.contributor.authorGugala, Natalie
dc.contributor.committeememberHarrison, Joe J.
dc.contributor.committeememberLewis, Ian A.
dc.contributor.committeememberShimizu, George K. H.
dc.contributor.committeememberMulvey, Michael
dc.date2019-11
dc.date.accessioned2019-07-30T14:26:11Z
dc.date.available2019-07-30T14:26:11Z
dc.date.issued2019-07-25
dc.description.abstractIt is fundamental to understand the mechanisms by which a toxicant is capable of poisoning the bacterial cell or resistance is developed. The mechanisms of actions of many antimicrobials such as metal-based compounds are not fully understood, yet, the development of these agents continues. Despite the essentiality of metals in the biochemistry of life, both non-essential and essential metals have been used as antimicrobials for agricultural and medical purposes for thousands of years. Applications include wound dressings, nanoparticles, antiseptic formulations, combination treatments, polymers and nanocomposites, among many more. Many of these have proven to be effective at controlling and eradicating microbial populations at low concentrations. Currently, studies in this field largely focus attention on developing new formulations and utilities for metal-based antimicrobials. The identity of the cellular targets that are involved in metal resistance and toxicity are known to a lesser degree. This current knowledge gap potentiates the progression of antimicrobial resistance since there is an incomplete understanding of metal action in microorganisms. Previous studies that have directed efforts toward these fundamental questions have failed to provide a comprehensive depiction of the global cellular effects of metal exposure; the literature is often replete with contradicting reports. Based on the aforementioned, we sought to answer the fundamental question – how do the mechanisms of metal toxicity and resistance compare in bacteria? We observed that the efficacies of metal ions varied between bacterial species and isolates of the same species. By means of the Keio collection, this comparison was validated by demonstrating that silver, copper and gallium act differently in Escherichia coli. Here, we presented a list of novel resistant and sensitive gene hits that may be involved in metal action. These experiments were performed under sublethal prolonged metal exposure, rather than acute shock. Resistance mechanisms range from efflux, iron-sulfur cluster maintenance, DNA repair, nucleotide biosynthesis to tRNA modification, and sensitive pathways include biomolecule import, NAD+ synthesis, amino acid biosynthesis, sulfur assimilation, electron transport, carbon metabolism and outer membrane maintenance, amongst others. To mitigate the improper use of metal-based antimicrobials, it is imperative that we understand precisely how these agents are able to eradicate bacterial cells and what are the accompanying mechanisms of resistance, particularly as development and use expands.en_US
dc.identifier.citationGugala, N. (2019). Comparing the mechanisms of metal action in bacteria: insight into novel genes involved in silver, gallium and copper resistance and toxicity in Escherichia coli (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/36779
dc.identifier.urihttp://hdl.handle.net/1880/110682
dc.language.isoengen_US
dc.publisher.facultyScienceen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectMetal resistance and toxicityen_US
dc.subjectBacteriaen_US
dc.subjectEscherichia colien_US
dc.subjectSystems Biologyen_US
dc.subjectMetal-based antimicrobialsen_US
dc.subjectSilveren_US
dc.subjectGalliumen_US
dc.subjectCopperen_US
dc.subject.classificationEducation--Sciencesen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationMicrobiologyen_US
dc.subject.classificationBiochemistryen_US
dc.titleComparing the mechanisms of metal action in bacteria: insight into novel genes involved in silver, gallium and copper resistance and toxicity in Escherichia colien_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineBiological Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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