Browsing by Author "Gugala, Natalie"

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    Comparing the mechanisms of metal action in bacteria: insight into novel genes involved in silver, gallium and copper resistance and toxicity in Escherichia coli
    (2019-07-25) Gugala, Natalie; Turner, Raymond Joseph; Harrison, Joe J.; Lewis, Ian A.; Shimizu, George K. H.; Mulvey, Michael
    It 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.
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    The efficacy of different antimicrobial metals at preventing the formation of, and eradicating bacterial biofilms of pathogenic indicator strains.
    (Nature, 2017-02-15) Gugala, Natalie; Lemire, Joe A.; Turner, Raymond J.
    The emergence of multidrug resistant pathogens and the prevalence of biofilm-related infections have generated a demand for alternative antimicrobial therapies. Metals have not been explored in adequate detail for their capacity to combat infectious disease. Metal compounds can now be found in textiles, medical devices, and disinfectants – yet, we know little about their efficacy against specific pathogens. To help fill this knowledge gap, we report on the antimicrobial and antibiofilm activity of seven metals; silver, copper, titanium, gallium, nickel, aluminum and zinc against three bacterial strains, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. In order to evaluate the capacity of metal ions to prevent the growth of, and eradicate biofilms and planktonic cells, bacterial cultures were inoculated in the Calgary Biofilm Device (MBEC™) in the presence the metal salts. Copper, gallium, and titanium were capable of preventing planktonic and biofilm growth, and eradicating established biofilms of all tested strains. Further, we observed that the efficacies of the other tested metal salts displayed variable efficacy against the tested strains. Further, contrary to the enhanced resistance anticipated from bacterial biofilms, particular metal salts were observed to be more effective against biofilm communities versus planktonic cells. In this study, we have demonstrated that the identity of the bacterial strain must be considered prior to treatment with a particular metal ion. Consequently, as the use of metal ions as antimicrobial agents to fight multidrug resistant and biofilm related infections increases, we must aim for more selective deployment in a given infectious setting.