High-throughput discovery of novel antibiotics against nontuberculous mycobacteria

Nontuberculous mycobacteria(NTM) are a group of bacteria responsible for over 100,000 deadly lung infections annually. Infections predominantly impact immunocompromised patients and the cystic fibrosis(CF) community, with ?10% of people with CF infected. High levels of intrinsic antimicrobial resistance and persistent infections have made these pathogens hard and often impossible to treat.

Current NTM therapeutic options involve intensive multi-drug regimens with low efficacy, severe side effects and high treatment burden. Average treatment costs range between £4k-£16k/year with additional healthcare spend of up to £10k. With increasing rates of resistance and no new antibiotic classes entering the market in the last 40 years, there is an urgent need for new antibiotic treatment options to combat NTM infections. The project aims to improve the clinical outlook, life expectancy and quality of life of NTM patients in the UK and globally.

80% of all antibiotics and 4 of 5 major classes used to treat NTM today derive from the ~1% of soil microbes which can be readily cultured in the laboratory. This bioresource has now been exhausted for novel antibiotics whilst efforts to discover new synthetic solutions have failed to fill the gap and have proven costly to develop(?£1Bn per novel antibiotic). Accessing the remaining 99% of uncultured microbes represents the best opportunity to discover new antibiotics.

Bactobio has developed a platform that combines synthetic biology, next-generation sequencing, and machine learning to culture previously unculturable microbes. So far, we have gained exclusive access to ?1,800 species. In this project, we will expand and screen our in-house library of unique microbial species for production of novel antibiotics against NTM. We have set an ambitious goal to find 3 promising antibiotic chemical compound candidates targeting NTM, thereby providing a compelling case for further investment from the pharmaceutical industry through licensing deals valued at ?£100Mn per compound.