Abstract: The antibiotic pipeline is broken, with a dearth of new antibiotics, a collapse in pharmaceutical company research, and the exhaustion of chemical diversity contained in pharma libraries. “The low hanging fruit from the antibiotic tree has probably already been picked and new sources of compounds are needed” (Nat Rev Drug Disc 2007 6, 29-40.). We desperately need to discover new antibiotics. Antibacterial drugs occupy a unique property space that is vastly different to drugs developed for other therapeutic areas, suggesting that commercially available chemical compounds lack the physicochemical properties ideal for activity against bacteria and, therefore, a varied source of chemical diversity needs to be investigated. We believe that there is an untapped resource contained in the laboratories of synthetic organic chemists: synthetic compounds prepared for other projects that have never been tested for their antimicrobial potential. These compounds may have been synthesised to validate new synthetic routes, develop new methodologies, create unusual structures or act on a different therapeutic target, but have never been screened for activity against microbes. We have created a Wellcome Trust-supported not-for-profit Open-Access pipeline, The Community for Open Antimicrobial Drug Discovery [CO-ADD], as a global screening initiative to uncover this significant and rich chemical diversity held outside of corporate screening collections (ACS Infect Dis, 2015, 1 285). CO-ADD provides unencumbered free antimicrobial screening for any interested researcher, building upon a suite of established in vitro and in vivo assays, medicinal chemistry and core researcher expertise, and aims to unearth fresh chemical diversity for the treatment of microbial infections.
In this talk I will describe the CO-ADD model and expand on the opportunities for chemists to test their compounds for antimicrobial activity. I will also present antimicrobial research programs within our group that exemplify other approaches to developing new antibiotics, including a potent new glycopeptide antibiotic for Gram-positive infections, new lipopeptide antibiotics active against highly resistant Gram-negative bacteria, bacterial detection using nanoparticles, and antibiotic-derived fluorescent probes.
Speaker's bio: Dr. Mark Blaskovich is a Program Coordinator for CO-ADD and a Senior Research Chemist at the Institute for Molecular Bioscience, The University of Queensland. Mark obtained his B.Sc (Honours Chemistry Co-op) from UVic, and PhD in synthetic organic chemistry at the University of Waterloo (Canada), developing new synthetic routes to unusual amino acids, then was a postdoctoral fellow with Prof Rod Rickards at the Research School of Chemistry, Australian National University. He is an experienced medicinal chemist who has worked in peptidomimetic drug design for 15 years at three biotech companies in the United States (Molecumetics, CEPTYR) and Australia (Mimetica). After successfully getting a melanocortin-5 receptor antagonist into clinical testing for the treatment of acne, he entered academia to focus on antimicrobial research and the development of new antibiotics. Mark is author of “The Handbook on Syntheses of Amino Acids”, has published over 40 papers, and is an inventor of 8 patent families encompassing over 25 granted patents.