Genome-scale functional genomics in Streptomyces species using CRISPR interference

大多数临床使用的抗生素来自链霉菌和其他密切相关的土壤细菌产生的化学物质。这些药物最初是在1940年至1960年抗生素发现的“黄金时代”被发现并引入临床的。在过去的半个世纪里，由于滥用，这些制剂的效用已经被侵蚀。因此，现在迫切需要发现新的抗生素来治疗耐药细菌感染。人们对抗菌剂耐药性的担忧与日俱增，再加上未能从大量合成化合物的筛选中找到新的线索，导致人们对天然产物的发现重新产生了兴趣。虽然我们对链霉菌生物学有很多了解，但不幸的是，我们的知识仍然存在重大差距，阻碍我们获得新药并以商业上可行的数量生产它们。我们认为，了解生物体基因组中每个基因的作用对于克服这一进展障碍至关重要。我们这项研究的目标是创造一种技术，快速并同时分析链霉菌物种基因组中编码的所有基因的重要性。我们的技术将使我们能够更详细地了解这些微生物，例如，通过学习生命所必需的基因。我们的技术有朝一日可能会被用于其他目的，例如，了解各种抗生素的生产是如何控制的，这样我们就可以更容易地获得新的化合物，它还将使制药业能够在更短的时间内设计出生产更多药物的链霉菌菌株。我们相信，我们的研究可以帮助更多的药物进入临床，可能会使它们更便宜，更广泛地获得。

The majority of clinically used antibiotics are derived from chemicals produced by Streptomyces species and other closely related soil bacteria. These drugs were primarily discovered and introduced into the clinic during a 'golden era' of antibiotic discovery that spanned 1940-1960. The utility of these agents has been eroded over the last half-century due to misuse. As a consequence, there is now an urgent need to discover new antibiotics to treat drug resistant bacterial infections. Growing concerns about resistance to antibacterial agents combined with the failure to find new leads from the screening of large libraries of synthetic compounds has led to a renewed interest in natural products discovery. Although we know a lot about Streptomyces biology, but unfortunately there are still major gaps in our knowledge that prevent us from accessing new drugs and producing them at the quantity required to be commercially viable. We believe that understanding the role of each gene in an organism's genome is essential to for overcoming this roadblock to progress. This goal of our research is to create technology to quickly and simultaneously analyse the importance of all genes encoded within the genome of a Streptomyces species. Our technology will allow us to understand these microorganisms in greater detail, for example, by learning the genes essential for life. Our technology could one day be used for other purposes, for instance, to learn how production of various antibiotics is controlled so we can access new compounds more easily, and it will also enable the pharmaceutical industry to engineer Streptomyces strains that produce more drug in a shorter timeframe. We believe our research could help make more medicines reach the clinic, possibly making them less expensive and more widely available.