Grant: Project Grant

Antibiotics underpin virtually all of modern medicine. These miracle drugs cure otherwise lethal infections, and allow complex surgeries, cancer treatments, and transplantations, amongst many other lifesaving medical interventions. The widespread emergence of anti-microbial resistant (AMR) bacteria poses a dire and ubiquitous threat to human health. The magnitude of this threat is now estimated by the World Health Organization to place millions of lives per year at risk, with economic costs in the many trillions of dollars. Most effective antibiotics were discovered as naturally-occurring compounds produced by microbes that live in the environment. However, the discovery of natural products has become ever-more arduous and cost-ineffective, such that no new antibiotic drug classes have been discovered for many decades. In parallel, the misuse of antibiotics in both human health care and agriculture has led to the rapid spread of many different types of antibiotic resistant bacterial species. To tackle the shortfall in antibiotic drug discovery, we have devised an innovative approach that uses laboratory-grown yeast to synthesize millions of natural product-like compounds, termed SynNPs for synthetic natural products. These SynNPs have the desirable chemical characteristics of natural products but have novel structures that will be less susceptible to known antibiotic resistance mechanisms. We propose to screen vast SynNP libraries in high-throughput to discover new antibiotic classes that target drug-resistant Staphylococcus aureus (MSRA), which causes many community- and hospital-acquired infections, as well as other prominent AMR bacterial pathogens. This novel synthetic natural product platform will enable a cost-effective, scalable and sustainable approach to mitigate the current antibiotic resistance crisis.