Delivering drugs via bacterial secretion systems

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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.