Filling the Void: How to find new antibiotics

The antibiotic pipeline is broken, with a dearth of new antibiotics accompanied by a collapse in pharmaceutical company research. We need to invest in research that can generate new antibiotics. This talk will provide an overview of the threat posed by antimicrobial resistance and illustrate drug discovery and development from an antimicrobial perspective, highlighting research from our laboratory that demonstrates several approaches that can be taken to discover new antibiotics:1) Rationally improve an existing antibiotic, where we have selectively modified vancomycin to more potently target bacterial cells, creating a novel Gram-positive glycopeptide antibiotic.2) Rediscover old antibiotics, by resurrecting a lipopeptide antibiotic first reported in the 1970s, and developing new analogs able to treat extensively-drug resistant (XDR) Gram-negative bacteria.3) Discover new antibiotics by ‘crowdsourcing’ chemical diversity from academic chemists around the world. Our Wellcome Trust-supported not-for-profit Open-Access pipeline, The Community for Open Antimicrobial Drug Discovery (CO-ADD), is a global screening initiative to uncover rich chemical diversity held outside of corporate screening collections. CO-ADD provides unencumbered free antimicrobial screening for any interested researcher.All three tactics have found success, and are at different stages of development. We have also developed an antibiotic-derived platform for detecting and imaging bacteria and bacterial infections, with potential to improve the diagnosis and treatment of infections. Our research demonstrates that it is possible to develop new antibiotics and alternate approaches to reduce antibiotic use, given sufficient time and resources.