Delivering drugs via bacterial secretion systems

描述（由申请人提供）：威斯康星大学麦迪逊分校最近发起了一项新的倡议，威斯康星抗菌研究项目（WisPAR）。该项目旨在创造和培育抗菌药物发现的新途径。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，这些技术既可以延长现有抗生素的使用寿命，又可以作为新的、有针对性的替代品。我们的目标是应用从各个学科收集到的知识来开发更智能、可持续的微生物管理方法。这一途径的一个步骤是利用自然发生的细菌偶联过程的概念。基于细菌偶联技术（bbct）的目标是利用质粒生物学来对抗抗生素耐药细菌的上升趋势。全面而言，这些技术将利用高度减毒的细菌作为载体，将抗菌剂输送到致病菌中。BCBT是许多科学家60多年来积累的成果。构成该技术的所有单独组件都已被证明是可行的。在这里，我们建议生产新类别的偶联递送抗菌化合物，并测试它们对一组细菌病原体的活性，其中一些细菌已对所有临床相关抗生素产生耐药性。公共卫生相关性：在抗生素耐药细菌引起的持续健康危机面前保持领先地位的唯一方法是不断开发新的抗菌剂，最好是那些以全新的方式攻击病原体的抗菌剂。基于细菌偶联技术（bbct）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，我们建议鉴定属于一种新的抗菌化合物的分子，并测试一种新的方法来提供抗菌剂，特别是针对目标细菌。

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.