Antimicrobial innovation by Big Pharma has slowed to a crawl while an epidemic of antimicrobial-resistant infections surges, threatening the public health. The overarching goal ofthe Wisconsin Antimicrobial Drug Discovery and Development Center is to develop therapeutic countermeasures to tackle the antimicrobial resistance crisis. Based upon our preliminary data, we hypothesize that natural product exploration of symbiotic environments using complementary cutting-edge approaches will provide a new paradigm for discovery of novel antimicrobials targeting drug resistant infections. The Center proposes innovative conceptual and technical advances to overcome critical bottlenecks identified in traditional antimicrobial drug discovery platforms. The success of this endeavor is dependent upon the ability to predict antimicrobial effectiveness ofthe symbiotic natural products in humans. The In vivo Core will assess the in vivo microbiologic effectiveness, mammalian safety, pharmacokinetics and pharmacodynamics of promising novel natural product scaffolds from each Project (1, 2, 3) in the Center. The Core uses clinically relevant murine infection models with each ofthe target, drug-resistant pathogens - fungal and gram-positive and negative bacteria. The results from these Core activities will predict which compounds with promising in vitro activity against drug-resistant pathogens are likely to progress to a clinically useful antimicrobial drug. The core services will also provide data that answer the question: which of the novel discovery approaches employed by our three CETR projects best delivers lead antimicrobial compounds. Elucidation of optimal discovery strategies will yield a transformative and sustained impact on the development of new drugs.

Public Health Relevance

There are no effective therapies for the emerging resistant pathogens that are becoming an increasing threat to the public health. The goals of the Center are to provide new, broad spectrum antimicrobial agents through a collaborative focus on high value natural product leads produced by under-explored sources of biological diversity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI109673-04
Application #
9235234
Study Section
Special Emphasis Panel (ZAI1-LR-M)
Project Start
Project End
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
4
Fiscal Year
2017
Total Cost
$369,870
Indirect Cost
$124,109
Name
University of Wisconsin Madison
Department
Type
Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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