Genome-scale functional genomics in Streptomyces species using CRISPR interference

点击翻译按钮获取中文摘要

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.