High-throughput discovery of novel antibiotics against resistant pathogens

不到100年前，抗生素在临床上的应用延长了预期寿命？20年，并允许开发以前不可能的医疗干预措施。这些治疗方法现在面临着传播耐药性的风险，因为细菌不断进化以抵抗它们，这意味着我们目前的治疗方法变得越来越无效。有效抗生素的丧失对现代医疗保健产生了严重而深远的影响，从常规感染治疗和助产到手术和癌症治疗。抗菌素耐药性（AMR）是一个直接的医疗保健威胁，每年造成120万人死亡，预计如果不采取重大行动，每年将增加到1000万人。迫切需要新型抗生素，可以靶向导致危及生命的感染的耐药细菌。其中最具威胁性的病原体是鲍氏不动杆菌：世卫组织重点优先AMR病原体，负责？100万例病例和？每年有40万人死于耐药？百分之五十现在需要新的药物来对抗这些感染，但是与其他药物相比，发现的高成本和较低的商业回报意味着没有新的抗生素进入市场。30年来，80%的临床抗生素来自于历史上可以在实验室培养的~1%的微生物。这种生物资源现在已经耗尽了新的抗生素，而努力发现新的合成解决方案未能填补差距，并已证明昂贵的开发（？每种新型抗生素10亿英镑）。剩余99%的未培养微生物是发现新抗生素的最佳机会。在Bactobio，我们开发了一个结合合成生物学，下一代测序和机器学习的平台，以培养以前无法培养的微生物。到目前为止，我们已经获得了独家访问？1,700种未被探索的微生物（？在这个项目中，我们将扩大和筛选我们内部的独特微生物库，用于生产针对_A的新型抗生素。鲍曼尼。我们制定了一个雄心勃勃的目标，即找到2-5种有前途的候选抗生素，为制药行业通过许可交易进行进一步投资提供了令人信服的理由（预期交易价值？这个项目的产出将为以下方面提供真实的希望？50万人感染耐药_A.鲍曼不动杆菌--以及数百万患有相关感染的人。更广泛地说，该项目将为英国不断增长的生命科学部门提供推动力，并重新建立抗生素发现管道。

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.