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

细菌多重耐药机制：多金属（类）敏感性-耐受性和转化

• 批准号: RGPIN-2020-03877
• 负责人: Turner, Raymond
• 金额: $ 5.03万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744844
• 关键词: Bacterial; multi; resistance; mechanisms; metal

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?

我的NSERC资助的研究项目是植根于了解细菌的毒素抗性机制。我的团队提出了这样一个问题：“什么样的生物化学和生理学允许细菌在特定的化学基团中处理各种杀菌剂，而不是特定的化合物？”在这个信封下，本应用程序探索了细菌对多种金属的抗性/耐受性的遗传和生化机制，与利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有关，以及了解用作抗菌剂的金属。我们已经在生物化学机制方面取得了许多发现，并确定了对有毒金属敏感/耐受的基因。这项工作提供了证据，证明并非所有的金属都会产生相同的杀伤机制，这在文献中是错误的假设。为了跟进这些发现，本资助周期的方向是深入探索对银、铜和镓（已被批准为金属基抗菌剂）敏感和耐受性的共同基因。我们发现，在这些不同的金属之间，只有一小部分基因在敏感性或耐受性方面有重叠。我们将评估这些基因突变对其他14种有毒金属的影响，看看这些基因的反应有多普遍。此外，我们的目标是利用我们开发的化学基因组筛选来评估细菌对类金属氧离子的反应，特别是：硒，碲，砷和锑。迄今为止，很少甚至没有对暴露于这些类金属的细菌进行广泛的系统研究（代谢组学、基因组学、蛋白质组学），但这些正在演变或建立环境污染物，并变得越来越具有经济意义。由于我对金属离子污染修复的兴趣，我们发现了能够生物吸附金属的菌株；但除此之外，我们观察到他们将金属离子转化为纳米材料。这很快演变成一个研究细菌生物合成硒和碲纳米材料的项目。展望未来，我们的目标将是系统地探索微生物生理状态及其对生物源纳米材料生产的影响及其特性。我想了解它们生物合成的生物化学原理。一个令人兴奋的结果将是生物转化补救策略，它不仅将从废物/矿山/尾矿水中去除金属污染物，而且同时为光伏和电子产品生产增值有用的材料。这些研究的广泛范围是提供对细菌在不同有毒金属离子存在下受到挑战生长的反应的生化和分子微生物学理解，以及如何在没有特定金属抗性基因决定因素的情况下实现耐受性。我们想要回答的基本问题是——在基因组和生化水平上，多金属的敏感性和耐受性是什么样的？