摘要

从20世纪20年代后期Alexander Fleming发现青霉素开始，抗生素已经彻底改变了医学领域。他们每年挽救了数百万人的生命，缓解了痛苦和痛苦，甚至被用于预防传染病的预防。但是，我们现在已经到了危机中，即使是最简单的感染，许多抗生素也不再有效。这种感染通常导致住院次数增加，治疗失败和耐药性病原体持续存在。尤其值得关注的是耐甲氧西林金黄色葡萄球菌，艰难梭菌，多药和广泛耐药的结核分枝杆菌，淋病奈瑟菌，耐碳青霉烯类肠杆菌科的细菌和产生广谱β-内酰胺酶的细菌，如大肠杆菌。更糟糕的是，由于多种原因，新的有效抗生素的发现一直在稳步下降。其中包括成本增加，政府缺乏足够的支持，投资回报率低，监管障碍和仅仅放弃抗菌领域的制药公司。相反，许多人选择专注于开发将长期使用的药物，这将提供更大的利润和更多的投资回报。因此，现在迫切需要开发新的有用的抗生素以避免回到“抗生素前期时代”。一些潜在的抗生素发现机会包括更好的经济诱因，基因组挖掘，合理的代谢工程，组合生物合成和对地球生物多样性的进一步探索。

Beginning with the discovery of penicillin by Alexander Fleming in the late 1920s, antibiotics have revolutionized the field of medicine. They have saved millions of lives each year, alleviated pain and suffering, and have even been used prophylactically for the prevention of infectious diseases. However, we have now reached a crisis where many antibiotics are no longer effective against even the simplest infections. Such infections often result in an increased number of hospitalizations, more treatment failures and the persistence of drug-resistant pathogens. Of particular concern are organisms such as methicillin-resistant Staphylococcus aureus, Clostridium difficile, multidrug and extensively drug-resistant Mycobacterium tuberculosis, Neisseria gonorrhoeae, carbapenem-resistant Enterobacteriaceae and bacteria that produce extended spectrum β-lactamases, such as Escherichia coli. To make matters worse, there has been a steady decline in the discovery of new and effective antibiotics for a number of reasons. These include increased costs, lack of adequate support from the government, poor returns on investment, regulatory hurdles and pharmaceutical companies that have simply abandoned the antibacterial arena. Instead, many have chosen to focus on developing drugs that will be used on a chronic basis, which will offer a greater profit and more return on investment. Therefore, there is now an urgent need to develop new and useful antibiotics to avoid returning to the ‘pre-antibiotic era’. Some potential opportunities for antibiotic discovery include better economic incentives, genome mining, rational metabolic engineering, combinatorial biosynthesis and further exploration of the earth’s biodiversity.

https://www.nature.com/articles/ja201730