Elucidating the membrane properties regulating antimicrobial peptidebinding to bacterial vesicles
阐明调节抗菌肽与细菌囊泡结合的膜特性
基本信息
- 批准号:10796034
- 负责人:
- 金额:$ 45.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-15 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAffinityAntibioticsBacteriaBasic ScienceBindingBinding ProteinsBiochemicalBiogenesisBiological AssayBiophysicsCell membraneCellsCharacteristicsChargeCollaborationsCommunicationCritical ThinkingDevelopmentEffectivenessExcisionFoundationsFutureGoalsGram-Negative BacteriaGrowthHeterogeneityImmune responseInfectionLipidsLipopolysaccharidesLiposomesMeasurementMembraneMembrane ProteinsMethodsMicroscopyMissionModelingNational Institute of General Medical SciencesNatureParentsPeptide AntibioticsPeptidesPhospholipidsPlayPreventionProcessPropertyProteinsResearchResearch PersonnelRoleSurfaceSurface Plasmon ResonanceTechniquesTestingTherapeutic AgentsVariantVesicleVisualizationWorkamphiphilicityantimicrobialantimicrobial peptidebiophysical techniquescathelicidin antimicrobial peptidechemical propertyclinical translationdesigndisease diagnosisfluorescence imaginggraduate studentinsightlight scatteringnext generationnovelperiplasmphysical propertypreventresponsesaturated fatskillsstudent mentoringundergraduate studentvesicular releasezeta potential
项目摘要
Project Summary
Antimicrobial peptides (AMPs), such as LL-37, have been proposed as potential next-generation
antibiotics due to their ability to bind to and disrupt the bacterial cell membrane. However, their use has
been limited by several factors, including inactivation by binding to bacterial outer membrane vesicles
(OMVs). OMVs are derived from the outer membrane (OM) of Gram-negative bacteria and therefore
have a similar membrane composition as the OM. OMVs are heterogeneous in their physical and
chemical properties, including size, charge, and lipid and protein composition, even among OMVs
produced by the same parent bacterium. Traditional methods to study protein/peptide interactions with
OMVs use bulk measurements, which result in ensemble averages that can obscure the influence OMV
heterogeneity has on these interactions. We have developed several approaches that enable us to study
protein-lipid interactions in OMVs on single-vesicle and subpopulation levels, which we will use in this
project to uncover the specific properties that regulate LL-37 binding to OMVs. We will first use liposomes
with controlled compositions to identify the roles of vesicle size, charge, lipid saturation, and LPS
composition in LL-37 binding. Next, we will use OMVs with varying sizes and charges to relate LL-37
affinity to the OMVs’ ability to protect bacterial cells from the activity of LL-37. Finally, we will investigate
how the properties of OMVs change upon exposure of the bacteria to LL-37 and how these changes
affect LL-37 binding to OMVs. Undergraduate and graduate students will be highly involved in all of the
proposed studies, and the Investigators are committed to mentoring these students to maximize their
development of technical, critical thinking, and communication skills. We anticipate that the results
generated from this project will inform the future design of more effective AMPs.
项目概要
抗菌肽 (AMP),例如 LL-37,已被提议作为潜在的下一代
抗生素,因为它们能够结合并破坏细菌细胞膜。然而,它们的使用已
受到多种因素的限制,包括通过与细菌外膜囊泡结合而失活
(OMV)。 OMV 源自革兰氏阴性菌的外膜 (OM),因此
具有与 OM 相似的膜成分。 OMV 的物理和结构是异质的
化学特性,包括大小、电荷、脂质和蛋白质组成,甚至在 OMV 中也是如此
由同一亲本细菌产生。研究蛋白质/肽相互作用的传统方法
OMV 使用批量测量,这会导致整体平均值掩盖 OMV 的影响
异质性对这些相互作用有影响。我们开发了几种方法,使我们能够研究
OMV 中单囊泡和亚群水平上的蛋白质-脂质相互作用,我们将在本研究中使用
项目旨在揭示调节 LL-37 与 OMV 结合的特定特性。我们首先使用脂质体
通过控制成分来确定囊泡大小、电荷、脂质饱和度和 LPS 的作用
LL-37 结合中的组成。接下来,我们将使用不同大小和电荷的 OMV 来关联 LL-37
与 OMV 保护细菌细胞免受 LL-37 活性影响的能力的亲和力。最后,我们将调查
当细菌暴露于 LL-37 时,OMV 的特性如何发生变化以及这些变化是如何发生的
影响 LL-37 与 OMV 的结合。本科生和研究生将高度参与所有的工作
拟议的研究,研究人员致力于指导这些学生最大限度地发挥他们的能力
技术、批判性思维和沟通技巧的发展。我们预计结果
该项目产生的结果将为未来设计更有效的 AMP 提供信息。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Nathan J. Wittenberg其他文献
Plasmonic nanopore arrays for characterizing the binding of myelin growth promoting igm antibodies to supported lipid bilayers
用于表征促进髓磷脂生长的 igm 抗体与支持的脂质双层的结合的等离子体纳米孔阵列
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
Nathan J. Wittenberg;H. Im;A. Warrington;Moses Rodriguez;Sang‐Hyun Oh - 通讯作者:
Sang‐Hyun Oh
Excitation of Fluorescent Lipid Probes Accelerates Phospholipid Vesicle Rupture and Supported Lipid Bilayer Formation
- DOI:
10.1016/j.bpj.2018.11.484 - 发表时间:
2019-02-15 - 期刊:
- 影响因子:
- 作者:
Ashley M. Baxter;Nathan J. Wittenberg - 通讯作者:
Nathan J. Wittenberg
Curvature Elasticity‐Driven Leaflet Asymmetry and Interleaflet Raft Coupling in Supported Membranes
曲率弹性驱动的小叶不对称性和支撑膜中的小叶间筏耦合
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:5.4
- 作者:
Yong‐Sang Ryu;Luke R. Jordan;Nathan J. Wittenberg;Sang Moon Kim;Daehan Yoo;Cherlhyun Jeong;A. Warrington;Moses Rodriguez;Sang‐Hyun Oh;S. Lee - 通讯作者:
S. Lee
The Effects of Photosensitized Lipid Oxidation on Supported Lipid Bilayer Formation and Membrane Deformation
- DOI:
10.1016/j.bpj.2019.11.2204 - 发表时间:
2020-02-07 - 期刊:
- 影响因子:
- 作者:
Ashley M. Baxter;Nathan J. Wittenberg - 通讯作者:
Nathan J. Wittenberg
Mid-infrared nanoplasmonics for label-free real-time biosensing of proteins and lipid membranes
用于蛋白质和脂质膜的无标记实时生物传感的中红外纳米等离子体
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
D. Etezadi;O. Limaj;Nathan J. Wittenberg;Daniel Rodrigo;Daehan Yoo;Sang‐Hyun Oh;H. Altug - 通讯作者:
H. Altug
Nathan J. Wittenberg的其他文献
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{{ truncateString('Nathan J. Wittenberg', 18)}}的其他基金
Microfluidic nanoarrays for high-throughput analysis of biological nanostructures
用于生物纳米结构高通量分析的微流控纳米阵列
- 批准号:
10019578 - 财政年份:2019
- 资助金额:
$ 45.7万 - 项目类别:
Microfluidic nanoarrays for high-throughput analysis of biological nanostructures
用于生物纳米结构高通量分析的微流控纳米阵列
- 批准号:
9805917 - 财政年份:2019
- 资助金额:
$ 45.7万 - 项目类别:
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