Probing How Living Bacterial Membranes Control Small Molecule Uptake

探究活细菌膜如何控制小分子摄取

• 批准号: 10276142
• 负责人: Tessa Rae Calhoun
• 金额: $ 35.9万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10276142
• 关键词: Address; Adsorption; Antibiotic Resistance; Antibiotics; Bacteria; Behavior; Binding; Biological Models; Cell Wall; Cell membrane; Cells; Dependence; Drug Design; Generations; Goals; Individual; Maps; Mediating; Membrane; Methodology; Microbial Biofilms; Microscopy; Movement; Research; Role; Spectrum Analysis; Techniques; Tetracyclines; combat; experimental study; improved; insight; new technology; programs; second harmonic; small molecule; success; uptake

Project Summary/Abstract Our research program aims to directly probe how the complexity of living bacterial membranes impacts the adsorption, transport, and domain association of small molecules, including antibiotics. To address these points, we will leverage nonlinear spectroscopy and microscopy techniques, specifically second harmonic generation, to map the dynamic behavior. A key to our methodology is the ability to conduct the proposed experiments on living cells instead of model systems. For the next 5 years, our program goals are to (1) extract the key factors that influence the adsorption and membrane organization of small molecule membrane probes, (2) quantitatively assess the adsorption of tetracycline antibiotics and manipulate their movement within and through the membranes of different species of bacteria, and (3) examine the spatial dependence of small molecule-membrane interactions on individual bacteria as well as within biofilms. Together these studies will elucidate the role of how parameters including curvature, membrane domains, and the cell wall mediate small molecule uptake. We envision that this insight will provide new directions in the continued pursuit of improved antibiotics.

项目总结/摘要 我们的研究计划旨在直接探索活细菌膜的复杂性如何影响细胞膜。 吸附，运输和小分子，包括抗生素域协会。解决这些 点，我们将利用非线性光谱和显微镜技术，特别是二次谐波 生成，以映射动态行为。我们的方法的关键是能够进行拟议的 用活细胞做实验而不是模型系统。未来5年，我们的目标是 (1)提取影响小分子吸附和膜组装的关键因素 膜探针，（2）定量评估四环素类抗生素的吸附，并操纵其 在不同种类的细菌的膜内和通过膜的运动，以及（3）检查空间 小分子-膜相互作用对单个细菌以及生物膜的依赖性。 这些研究将共同阐明包括曲率，膜域， 细胞壁介导小分子摄取。我们设想这种洞察力将提供新的方向 继续追求改良的抗生素