Delivering drugs via bacterial secretion systems

通过细菌分泌系统输送药物

• 批准号: 7739236
• 负责人: MARCIN S FILUTOWICZ
• 金额: $ 18.08万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739236
• 关键词: Address; Amber; Amino Acids; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Attenuated; Bacteria; Bacteriophages; Biological Assay; Biology; Carrier Proteins; Categories; Cells; Collection; Containment; DNA; DNA Primase; Discipline; Escherichia coli; Evaluation; Genes; Genetic Conjugation; Genetically Modified Organisms; Goals; Government; Growth; Health; Individual; Kinetics; Knowledge; Laboratories; LacZ Genes; Libraries; Longevity; Measures; Membrane Proteins; Methods; Microbe; Mutation; One-Step dentin bonding system; Pathway interactions; Persons; Pharmaceutical Preparations; Phenotype; Plasmids; Process; Production; Proteins; RNA; RNA Phages; Reporting; Research; Resistance; Resources; Risk; Route; Scientist; Structure; System; Technology; Temperature; Testing; Therapeutic; Toxic effect; Toxin; Transfer RNA; Universities; Wisconsin; Work; antimicrobial; antimicrobial drug; aptamer; base; clinically relevant; combat; design; killings; male; novel; novel strategies; pathogen; pathogenic bacteria; plasmid DNA; polypeptide; public health relevance; research study; tool; uptake

DESCRIPTION (provided by applicant): University of Wisconsin-Madison has recently launched a new initiative, the Wisconsin Project for Antimicrobial Research (WisPAR). This project is designed to create and nurture novel pathways to antimicrobial discovery. The resource partnership created and nurtured by WisPAR will be critical for rapidly developing antimicrobial technologies with the capacity to both extend the lifespan of current antibiotics and to act as new and appropriately targeted alternatives. Our goal is to apply collected knowledge from a variety of disciplines to develop smarter, sustainable approaches to microbe-management. One step on this pathway is a concept utilizing naturally occurring process of bacterial conjugation. The objective of the Bacterial Conjugation-Based Technologies (BCBT) is to exploit plasmid biology to combat the rising tide of antibiotic-resistant bacteria. In its full breadth, these technologies will utilize highly attenuated bacteria as vehicles for delivering antimicrobial agents into pathogenic bacteria. BCBT benefits from the accumulated work of many scientists over a period of six decades. All of the individual components that comprise the technology have been demonstrated to be feasible. Here we propose production of new categories of conjugationally-delivered antimicrobial compounds and test their activity against a group of bacterial pathogens, some of which have become resistant to all clinically relevant antibiotics PUBLIC HEALTH RELEVANCE: The only way to stay ahead of the ongoing health crisis caused by antibiotic resistant bacteria is to continually develop new antibacterial agents, preferably ones that attack pathogens in entirely new ways. Bacterial Conjugation-Based Technologies (BCBT) will exploit plasmid biology to develop smarter, sustainable approaches to microbe-management. Here we propose to identify molecules belonging to a new category of antimicrobial compounds and to test a novel method for delivering antimicrobials, specifically, to target bacteria.

描述（由申请人提供）：威斯康星大学麦迪逊分校最近推出了一项新的倡议，威斯康星州抗菌研究项目（WisPAR）。该项目旨在创建和培育抗菌药物发现的新途径。由WisPAR创建和培育的资源伙伴关系对于快速开发抗菌技术至关重要，这些技术既能延长现有抗生素的使用寿命，又能作为新的、适当针对性的替代品。我们的目标是应用从各个学科收集的知识，开发更智能，可持续的微生物管理方法。该途径的一个步骤是利用天然存在的细菌接合过程的概念。基于细菌偶联的技术（BCBT）的目标是利用质粒生物学来对抗不断上升的抗生素耐药细菌。在其全部范围内，这些技术将利用高度减毒的细菌作为载体，将抗菌剂输送到病原菌中。BCBT受益于许多科学家六十年来积累的工作。构成该技术的所有单个组件都已被证明是可行的。在这里，我们建议生产新类别的结合递送的抗微生物化合物，并测试它们对一组细菌病原体的活性，其中一些已经对所有临床相关抗生素产生耐药性公共卫生相关性：保持领先于抗生素耐药细菌引起的持续健康危机的唯一方法是不断开发新的抗菌剂，最好是以全新方式攻击病原体的抗菌剂。基于细菌结合的技术（BCBT）将利用质粒生物学来开发更智能，可持续的微生物管理方法。在这里，我们建议确定属于一类新的抗微生物化合物的分子，并测试一种新的方法来提供抗微生物剂，特别是目标细菌。