Grant: Project Grant

The COVID-19 pandemic has revealed our continued vulnerability to infectious diseases and the importance of discovering and characterizing new anti-infective agents. Antibiotic resistance, where bacteria have acquired or evolved resistance to our existing drugs, has been termed a "silent pandemic". Consequently, there is a great need for research into new anti-infective drug targets and lead compounds. Most antibiotics and antifungal agents originate in the specialized metabolites, also known as natural products, that are produced by environmental bacteria and fungi. Over the past two decades, my lab has collected over 15,000 of these environmental microorganisms that we have successfully used to identify new antibiotics, antifungal agents, antimalarial compounds, anti-cancer agents, and inhibitors of antibiotic resistance. We propose to exploit this unique resource and our momentum and deep experience in this area to identify, characterize, and evaluate novel anti-infective molecules. We have shown that such compounds can be used to further our understanding of infectious organisms and their vulnerabilities and can act as leads for new therapies. Specifically, we will probe our collection of natural product producers to discover new antibiotics targeting human pathogens and new anti-mycobacterial agents that are directed to disease such as tuberculosis. The outcomes of this project will be several new molecules that can act as probes of the biology of pathogenic infectious organisms, deepening our understanding of their vulnerabilities. Our experience shows that these studies can also identify compounds with future applications as leads for new anti-infective therapeutic agents that can address the growing crisis in anti-infective drug resistance.