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Filling the Void: How to find new antibiotics

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The antibiotic pipeline is broken, with a dearth of new antibiotics accompanied by a collapse in pharmaceutical company research.[1] 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]

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]

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.[4] 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.

[1] Butler, Blaskovich, Cooper, Antibiotics in the clinical pipeline J. Antibiotics 2017, 3-24.

[2] Blaskovich et al, Nature Communications (2018) 9, 22.

[3] Velkov et al, Cell Chemical Biology, (2018), 25, in press

[4] Blaskovich et al Helping chemists discover new antibiotics ACS Infect. Dis. 2015, 285-287.

Dr Mark Blaskovich is an antibiotic hunter based at the Centre for Superbug Solutions in the Institute for Molecular Bioscience at The University of Queensland, and cofounder of the Community for Open Antimicrobial Drug Discovery, a global antibiotic discovery initiative. Since starting at UQ in 2010, Mark has been working on developing new antibiotics to treat drug resistant pathogens and the use of modified antibiotics to detect bacterial infections. He has initiated a research program focused on a theranostic platform that chemically links existing antibiotics with other antibiotics, antibiotic adjuvants, antibodies, magnetic nanoparticles and imaging moieties, creating hybrid constructs with therapeutic and diagnostic potential. Mark has extensive medicinal chemistry expertise and over 15 years of industrial drug development experience at three biotech companies, most recently as Chief Operating Officer of Mimetica where he developed a drug that recently completed Phase 2 human clinical trials for treatment of acne. He has published over sixty research articles, authored ‘The Handbook on Syntheses of Amino Acids’, and is an inventor on eleven patent families with over 100 granted and pending applications.

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