Research Initiation Award: Antagonistic Bacteriophage and Metal Combination Treatment to Combat the Spread of Antimicrobial Resistance

研究启动奖为传统黑人学院和大学的初级和中期职业教师提供支持，他们正在建立新的研究项目或重新指导和重建现有项目。期望该奖项有助于提高教师的研究能力和效率，改善所在机构的研究和教学，并使本科生参与研究经验。本研究旨在确定和阐明大肠杆菌的进化适应性，以及它们的获得性耐药突变如何影响它们对常见抗生素的适应性和易感性。进化的权衡在自然界中无处不在，对生物体的适应，特别是对恶劣环境的适应有着重要的影响。进化权衡和/或权衡的发现对于确定噬菌体作为抗菌剂的可持续性至关重要。了解这些相互作用对于解决抗菌素耐药性这一全球卫生问题至关重要。该项目旨在探索由于对一类天然抗菌剂噬菌体获得性耐药性而发生的潜在进化权衡和共选择机制，并探索它们对金属耐药性的潜在权衡，特别是过量的铁。主要的焦点将是大肠杆菌对T4噬菌体的进化适应，以及获得性噬菌体抗性突变如何影响细菌的适应性和对金属和常见抗生素的敏感性。由于噬菌体T4和铁（III）具有相似的靶标，包括用于噬菌体附着和铁进入的外膜蛋白，因此噬菌体T4-铁（Fe3+）抗性相互作用具有重要意义。这项工作旨在发现细菌群体中是否发生拮抗相互作用，其中噬菌体抗性降低金属抗性（反之亦然）。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing programs. It is expected that the award helps to further the faculty member's research capability and effectiveness, improves research and teaching at the home institution, and involves undergraduate students in research experiences. This study seeks to determine and elucidate the evolutionary adaptationof the Escherichia coli bacteria and how their acquired resistance mutations influence their fitness and susceptibility to common antibiotics.Evolutionary trade-offs are ubiquitous in nature and have important consequences for organismal adaptation, especially to harsh environments. The discovery of evolutionary trade-offs and/or trade-ups is imperative to determine the sustainability of bacteriophages as antimicrobial agents. Understanding these interactions is essential in addressing the global health concern of antimicrobial resistance. This project seeks to explore potential evolutionary trade-offs and co-selection mechanisms that occur because of acquired resistance to a class of natural antibacterial agents, bacteriophages, and to explore their potential trade-offs against metal resistance, specifically excess amounts of iron. The primary focus will be on the evolutionary adaptation of Escherichia coli to bacteriophage T4 and how acquired phage resistance mutations influence bacterial fitness and susceptibility to metals and common antibiotics. Bacteriophage T4-Ferric iron (Fe3+) resistance interactions are of significant interest since phage T4 and iron (III) share similar targets including outer membrane proteins used for phage attachment and iron entry. The work seeks to discover if antagonistic interactions, in which phage resistance reduces metal resistance (or vice versa) occur within bacterial populations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.