Bacterial multi-resistance mechanisms: multi-metal(loid) sensitivity-tolerance and transformations

点击翻译按钮获取中文摘要

My NSERC funded research program is rooted in understanding toxin resistance mechanisms in bacteria. My group asks the question: "What biochemistry and physiology allow bacteria to deal with a variety of biocide agents within a specific chemical group, rather than a specific compound?" Under this envelope, this application explores the genetic and biochemical mechanisms of multi-metal resistance/tolerance in bacteria with a connection to using bacteria in bioremediation of metals and metalloid pollutants from contaminated environments as well as understanding metals used as antimicrobials. We have made a number of discoveries around the biochemical mechanisms and identified genes responsible for sensitivity/tolerance towards toxic metals. This work provided evidence that not all metals give rise to the same killing mechanism which has been incorrectly assumed in the literature. To follow up on these discoveries, this grant cycle's directions are to explore deeper the shared genes of sensitivity and tolerance towards silver, copper and gallium, which are approved as metal-based antimicrobials. We discovered there was only a small set of genes that overlapped between these different metals for sensitivity or tolerance. We will evaluate the mutants of these genes to 14 other toxic metals to see how universal these genes responses are. Additionally, we aim to use our developed chemical genomic screen to evaluate bacterial response to oxyanions of metalloids, particularly: selenium, tellurium, arsenic and antimonite. Little to no broad system studies (metabolomics, genomics, proteomics) have been performed on bacteria exposed to these metalloids to date, yet these are evolving or established environmental pollutants as well as becoming more economically relevant. From my interest in metal ion pollution remediation, we discovered strains capable of biosorption of the metal; but beyond this, we observed they converted the metal ion into nanomaterials. This has quickly evolved into a project studying bacterial biosynthesis of selenium and tellurium nanomaterials. Moving forward, the aim will be to systematically explore microbial physiological states and their influence on biogenic nanomaterial production and their characteristics. I want to understand the biochemistry of their biosynthesis. An exciting outcome would be bioconversion remediation strategies that will not only remove the metal pollutant from waste/mine/tailings water but produce value-added useful materials for photovoltaics and electronics at the same time. The broad scope of these studies is to provide a biochemical and molecular microbiology understanding of the response of a bacterial to being challenged to grow in the presence of different toxic metal ions and how tolerance is achieved without specific metal resistance gene determinants. The fundamental question we want to answer - What does multi-metal sensitivity and tolerance look like at the genomic and biochemical level?