Constructing and Deconstructing Antibiotics

Timothy Wencewicz, Washington University in St. Louis

Contrary to popular belief, antibiotic resistance is not man made and is not always a bad thing. Microbes have been making and breaking antibiotics for hundreds of millions of years. Antibiotic resistance and antibiotic biosynthesis in the natural world have reached steady state. Anthropogenic use of antibiotics can tip the equilibrium towards antibiotic resistance in certain environments including farms and hospitals where antibiotics are needed most. Despite our entry into the era of antibiotic resistance, an argument will be made that the future is bright for antibiotics thanks to Nature’s rich chemical inventory. Lessons from microbes and the antibiotics they produce provide foresight into the existing methods for constructing and destructing antibiotics to manage antibiotic resistance. Two case studies from my laboratory demonstrating the power of antibiotic foresight will be highlighted in this lecture: 1) tetracycline inactivating enzymes – a case of antibiotic destruction; 2) non-ribosomal peptide beta-lactones – a case of antibiotic construction.

Presented as part of the Center for Clinical Pharmacology Seminar Series.