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

我的NSERC资助的研究项目植根于了解细菌的毒素抗性机制。我的小组提出了一个问题：“什么生物化学和生理学允许细菌处理特定化学组中的各种杀生物剂，而不是特定的化合物？“在这个信封下，该应用程序探索了细菌中多金属抗性/耐受性的遗传和生化机制，与使用细菌对污染环境中的金属和类金属污染物进行生物修复以及理解用作抗菌剂的金属有关。我们已经在生化机制方面取得了许多发现，并确定了负责对有毒金属敏感性/耐受性的基因。这项工作提供的证据表明，并非所有金属都会产生相同的杀伤机制，这在文献中被错误地假设。 为了跟进这些发现，本资助周期的方向是更深入地探索对银、铜和镓的敏感性和耐受性的共同基因，这些基因被批准为金属基抗菌剂。我们发现只有一小部分基因在这些不同的金属之间重叠，以获得敏感性或耐受性。我们将评估这些基因的突变体对其他14种有毒金属的反应，看看这些基因的反应有多普遍。此外，我们的目标是使用我们开发的化学基因组筛选来评估细菌对含氧阴离子的类金属，特别是：硒，碲，砷和锑。迄今为止，对暴露于这些类金属的细菌进行了很少或没有广泛的系统研究（代谢组学，基因组学，蛋白质组学），但这些都是不断发展或建立的环境污染物，并且变得更加经济相关。 从我对金属离子污染修复的兴趣出发，我们发现了能够生物吸附金属的菌株;但除此之外，我们观察到它们将金属离子转化为纳米材料。这已经迅速发展成为一个研究硒和碲纳米材料的细菌生物合成的项目。展望未来，目标将是系统地探索微生物的生理状态及其对生物纳米材料生产及其特性的影响。我想了解它们生物合成的生物化学。一个令人兴奋的结果将是生物转化修复策略，不仅可以从废物/矿山/尾矿水中去除金属污染物，还可以同时为光化学和电子产品生产增值的有用材料。这些研究的广泛范围是提供一个生物化学和分子微生物学的理解，细菌的反应被挑战，在不同的有毒金属离子的存在下生长，以及如何实现耐受性没有特定的金属抗性基因决定因素。我们想要回答的基本问题是：在基因组和生物化学水平上，多金属敏感性和耐受性是什么样的？

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?