| 项目编号: | 1554417
|
| 项目名称: | CAREER: Targeting Virulence Factor Delivery for the Development of Antibacterial Agents |
| 作者: | Angela Brown
|
| 承担单位: | Lehigh University
|
| 批准年: | 2016
|
| 开始日期: | 2016-06-01
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| 结束日期: | 2021-05-31
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| 资助金额: | 512000
|
| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
|
| 英文关键词: | virulence factor
; omv
; pi
; delivery
; development
; bacterial infection
; virulence
; omv delivery
; goal
; targeting virulence
; project
; pathogenic bacterium
; specific factor
; career proposal address
; related technical career
|
| 英文摘要: | 1554417
Brown, Angela C.
The rise of antibiotic resistance threatens our ability to treat even minor bacterial infections. With few new drugs in development and rates of resistance increasing, we urgently need new, nontraditional approaches to fight pathogenic bacteria. The goal of this project is to target the delivery of molecules that facilitate the virulence of pathogenic bacteria as a novel approach to the treatment of bacterial infections. Rather than targeting some essential life process to kill the bacteria directly as traditional antibiotics due, the PI intends to target those processes that allow the pathogen to settle in the host. This CAREER proposal addresses two goals outlined by the United States CDC: to develop new approaches to the treatment of bacterial infections and to improve antibiotic stewardship. In addition to identifying unique targets for the development of novel antibiotics, the PI plans extensive outreach activities to demonstrate in a fun, hands-on manner, the danger of misusing antibiotics. The PI intends to further integrate the research with her educational goals by developing new courses at Lehigh University, providing undergraduate and graduate research opportunities, and developing a program for local Girl Scout troops to learn about STEM fields. The PI?s overall goals in these educational activities is to develop well-trained, interdisciplinary scientists and to encourage young women to
choose STEM majors and pursue related technical careers.
Pathogenic bacteria produce certain molecules, called virulence factors that allow them to thrive within the host. One mechanism used by Gram negative bacteria to transfer these factors to target cells is the production of outer membrane vesicles (OMVs), which bleb off from the outer membrane of the bacterium and encapsulate multiple virulence factors. The goal of this project is to characterize the
trafficking of these OMVs for the identification of shared mechanisms that can be blocked to inhibit virulence factor delivery. The overall hypothesis of the project is that toxins present on the surface of the OMV facilitate binding of the OMV to the target cells, and inhibition of this binding can be used to disrupt delivery of virulence factors. To investigate this hypothesis, the PI will study three representative organisms, enterotoxigenic Escherichia coli, Vibrio cholerae, and Bordetella pertussis. With these three organisms, she will first characterize the mechanisms by which bacterial toxins bind to the lipid components of the OMV and determine role of membrane properties in this interaction. This aim will be accomplished by studying the affinity of each toxin for specific lipids, using isothermal titration calorimetry. Next, she will study the interaction between OMVs and specific components of host cells, using calorimetric and microscopy techniques. Finally, with this information, she will design methods to prevent OMV delivery by blocking specific factors found to facilitate OMV delivery; this will allow the PI to inhibit the virulence of these organisms. Targeting virulence in this way represents a novel approach to treating bacterial infections, which is desperately needed due to our current lack of effective antibiotic strategies. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/92110
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Angela Brown. CAREER: Targeting Virulence Factor Delivery for the Development of Antibacterial Agents. 2016-01-01.
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