Probing How Living Bacterial Membranes Control Small Molecule Uptake

项目摘要/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 包括抗生素在内的小分子的吸附、运输和结构域关联。要解决这些问题 点，我们将利用非线性光谱和显微技术，特别是fi的二次谐波 生成，以映射动态行为。我们方法论的一个关键是能够执行建议的 在活细胞而不是模型系统上进行实验。未来5年，我们的计划目标是 (1)提取影响fl中小分子吸附和膜组织的关键因素 膜探针，(2)定量评估四环素类抗生素的吸附并操纵其 不同种类细菌的膜内和膜之间的运动，以及(3)检查空间 小分子-膜相互作用对单个细菌以及在生物fiLMS内的依赖性。 这些研究将共同阐明包括曲率、膜结构域、 细胞壁介导小分子摄取。我们设想，这一洞察力将提供新的方向 继续追求改良的抗生素。

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.