High-throughput discovery of novel antibiotics against resistant pathogens

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Introduction of antibiotics to the clinic less than 100 years ago extended life expectancies by ?20 years and permitted development of medical interventions which were previously impossible. These treatments are now at risk from spreading drug resistance as bacteria constantly evolve to resist them, meaning our current repertoire is becoming increasingly ineffective. Loss of effective antibiotics has severe and far-reaching consequences for modern healthcare, from routine infection treatments and midwifery to surgery and cancer treatments.Antimicrobial resistance (AMR) is an immediate healthcare threat, responsible for 1.2Mn deaths every year and expected to rise to 10Mn per year without significant action. There is an urgent need for novel antibiotics that can target resistant bacteria responsible for life-threatening infections. Among the most threatening pathogens is _Acinetobacter baumannii_: a WHO critical priority AMR pathogens, responsible for ?1Mn cases and ?400k deaths annually with resistance rates ?50%. New drugs are needed now to combat these infections, but high costs of discovery and lower commercial returns compared to other pharmaceuticals have meant that no novel antibiotics have reached the market in ?30 years.80% of all clinical antibiotics derive from the ~1% of microbes which could historically be 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.At Bactobio, we have developed a platform combining synthetic biology, next-generation sequencing and machine-learning to culture previously unculturable microbes. So far, we have gained exclusive access to ?1,700 unexplored microbes (?3% of species ever cultured) and our library is growing every week.In this project, we will expand and screen our in-house library of unique microbes for production of novel antibiotics against _A. baumannii_. We have set an ambitious goal to find 2-5 promising antibiotic candidates, providing a compelling case for further investment from the pharmaceutical industry through licensing deals (expected deal value ?£100Mn).Outputs from this project would provide real hope to ?500k individuals infected with drug-resistant _A. baumannii_ and the millions more with related infections. More broadly, this project will provide a boost to the UK's growing life sciences sector and re-establish the antibiotic discovery pipeline.