Characterizing the Evolutionary Behavior of Bacteria in the Presence of Iron Nanoparticles.

耐多药细菌的传播现在是现代社会的一个重要问题。例如，2012年，耐甲氧西林金黄色葡萄球菌(MRSA)在美国导致的死亡人数超过了艾滋病、乙肝和结核病的总和。为了解决这一问题，需要新的抗菌治疗方法。其中最有希望的是使用金属/金属氧化物纳米颗粒。然而，该领域的许多研究人员还没有考虑到细菌对金属和金属氧化物(银、铜、铁)的抗药性会像对传统抗生素那样快。这项研究项目将专门研究细菌对铁/氧化铁纳米颗粒产生抗药性的方法、速度和机制。为了研究细菌对铁毒性的抵抗力是如何产生的，PI建议利用一系列实验室实验进行基因组重新测序。这一知识将为更适当地使用这些抗菌剂提供科学数据，从而避免或最大限度地减少耐药性的发展。为了研究细菌如何对铁/氧化铁纳米颗粒产生抵抗力，PI将利用实验室实验，通过暴露于？×-Fe2O3(磁铁矿)和Fe3O4(磁铁矿)纳米颗粒来产生耐铁的大肠杆菌K-12 MG1655菌株。PI将利用不同的祖先菌株来衍生出两种不同类型的抗铁种群。其中一个祖先将没有先前的金属抗性，而第二个祖先将有白银抗性的历史。PI将使用全基因组重测序来检查祖先和抗铁衍生种群的基因组。这将允许PI测试以前存在的重金属抗性机制是否在发展对磁性氧化铁的抗性方面具有优势。这些实验还将允许PI测试基因组对亚铁(Fe2+)的适应是否不同于铁(Fe3+)毒性所产生的那些适应。该项目将提供关于细菌对金属/金属氧化物纳米颗粒产生耐药性的机制的关键的基于基因组的信息。所得数据将有助于研究人员开发基于纳米的干预措施来控制多重耐药细菌。控制耐药性发展的能力将提高金属/金属氧化物纳米颗粒潜在医疗用途的可持续性。这项研究可以通过阐明细菌耐药性的机制使科学界普遍受益，也可以通过减少传染病而使普通公众受益。这项研究将通过北卡罗来纳A&T州立大学(HBCU)和北卡罗来纳大学(UNC)格林斯伯勒分校(一家为少数族裔服务的机构)之间的合作，在纳米科学和纳米工程联合学院进行。该项目还将包括鼓励和指导科学和工程学科的代表不足的第一代大学生。

Graves1602593The spread of multidrug resistant bacteria is now a crucial concern for modern society. For example in 2012, methicillin resistant Staphylococcus aureus (MRSA) killed more people in the USA than AIDS, hepatitis B, and tuberculosis combined. To address this concern there is a need for novel antimicrobial treatments. One of the most promising of these is the use of metallic/metallic oxide nanoparticles. However, many researchers in this field have not considered the possibility that bacteria can evolve resistance to metals and metallic oxides (silver, copper, iron) as quickly as they did to traditional antibiotics. This research project will specifically study the methodology, speed, and mechanism by which bacterium can evolve resistance to iron/iron oxide nanoparticles. To examine how resistance to iron toxicity may arise in bacteria, the PI proposes to utilize a series of laboratory experiments with genomic resequencing. This knowledge will provide science-based data for more appropriate use of these antimicrobials so that the development of resistance is avoided or minimized. To examine how bacteria may evolve resistance to iron/iron oxide nanoparticles the PI will use laboratory experiments to produce iron resistant strains of E. coli K-12 MG1655 via exposure to ?×-Fe2O3 (maghemite) and Fe3O4 (magnetite) nanoparticles. The PI will utilize different ancestral strains to derive into the two different types of iron resistant populations. One of the ancestors will have no prior metal resistance and the second ancestor will have a history of silver resistance. The PI will use whole genome resequencing to examine the genomes of the ancestors and the iron-resistant derived populations. This will allow the PI to test whether previously existing heavy metal resistance mechanisms provide an advantage in the development of resistance to magnetic iron oxide. These experiments will also allow the PI to test whether the genomic adaptations to ferrous iron (Fe2+) are different from those adaptations engendered by ferric iron (Fe3+) toxicity. This project will provide crucial genomic-based information concerning the mechanisms by which bacteria evolve resistance to metal/metallic oxide nanoparticles. The resulting data will be useful for researchers developing nano-based interventions to control multi-drug resistant bacteria. The ability to control the development of resistance will improve the sustainability of potential medical uses of metallic/metallic oxide nanoparticles. This research could benefit both the scientific community in general by elucidating mechanisms of bacteria resistance and the general public by the reduction in infectious disease. This research will be conducted at the Joint School of Nanosciences and Nanoengineering through a partnership between North Carolina A &T State University (HBCU) and the University of North Carolina (UNC) Greensboro (a minority-serving institution). This project will also involve encouraging and mentoring underrepresented and first-generation college students in science and engineering disciplines