Project 3 Project Summary The human body is host to, and interacts with, a complex and dynamic community of microbes called the microbiome. One critical function of the human microbiome is to help protect its host from infection. In project three, we will identify members of the microbiome that can produce antibiotics that are active against drug resistant pathogens and safe for human use. Through the use of genomics, we predict that the human microbiome has the capacity to produce thousands of bioactive natural products that have not been characterized. At UW-Madison, we have several large and ongoing human microbiome studies that provide us access to thousands of samples from diverse populations of people for the isolation and screening of new antimicrobial molecules. We will isolate microbes derived from the human microbiome, determine their antimicrobial activity against Gram-negative and fungal pathogens, and apply our genomics and metabolomics approaches to predict molecules with new chemistry. Our project goals contribute to the mission of the Wisconsin Antimicrobial Drug Discovery and Development Center aiming to develop new therapeutics in response to the growing antimicrobial resistance crisis.