Antibiotic Discovery

The most important practical application of the cultivation platforms we developed is drug discovery.  For example, antibiotics discovery is at its lowest in decades, and the pipeline of novel candidate antimicrobials is dry.  Yet the rise of antibiotics resistance in common pathogens is one of the most important global health threats, already accounting for tens of thousands of lives in the Western world alone. The industry collapsed years ago because the cultivable minority of species have been overmined by 70+ years of extensive exploration of easy to cultivate strains.  Our technologies promise to reverse the trend by sampling the pool of microorganisms that have never been explored.  On this promise, Slava Epstein and Kim Lewis co-founded a start up company Novobiotic Pharamaceuticals LLC (http://www.novobiotic.com). The principal mission of the company is to discover and develop novel antibiotics from an entirely new source: formerly uncultivated microbial species.

pic2Over the past ten years, efforts of Novobiotic’s scientists are beginning to pay off.  Their highly novel, 50,000+ strong collection of new strains has been found to produce numerous novel bioactive compounds.  Of particular interest is teixobactin, whose discovery was reported in January 2015 (LL Ling, T Schneider, AJ Peoples, AL Spoering, I Engels, BP Conlon, AMueller, TF Schäberle, DE Hughes, SEpstein, MJones, L Lazarides, VA Steadman, DR Cohen, CR Felix, KA Fetterman, WP Millett, AG Nitti, AM Zullo, C Chen, K Lewis (2015) A new antibiotic kills pathogens without detectable resistance Nature 517: 455-459).

Teixobactin is a novel class of antimicrobials with a unique mode of action.  The latter explains its most intriguing and promising properties: the resistance to it cannot be found no matter the amount of efforts Novobiotic’s scientists apply such that no single resistant mutant has been detected.  This led to a wide coverage of the discovery by Nature, Science, other publications, BBC, NPR, National Geographic, and mass media in Germany, GB, France, Denmark, Sweden, Netherlands, China, S. Korean, and many other countries. Teixobactin is in preclinical development, which, if successful, may lead to human trials in 1.5-2 years.  If it becomes a drug, teixobactin will become the first new class of antibiotics discovered in 30 years.

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Teixobactin is not the only molecule in preclinical development at Novobiotic Pharmaceuticals.  Other noteworthy antimicrobial is lassomycin, a cyclic peptide with high activity specifically against Mycobacterium tuberculosis, the causative agent of tuberculosis (E Gavrish, CS Sit, S Cao, O Kandror, A Spoering, A Peoples, L Ling, A Fetterman, D Hughes, A Bissell, H Torrey, T Akopian, A Mueller, S Epstein, A Goldberg, J Clardy, K Lewis (2014) Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chemistry & biology 21: 509-518).

These and other discoveries highlight the promise of “uncultivable” microorganisms as a new source of novel bioactive compounds, and the cultivation platforms we have developed as tools to access and explore these microorganisms (Lewis, K., Epstein, S.S., D’Onofrio, A., and Ling, L.L. (2010). Uncultured microorganisms as a source of secondary metabolites. J. Antibiot. 63, 468–476).

 

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