The molecular basis of the action of the antibiotic simocyclinone D8 on DNA gyrase

抗生素是用来治疗细菌引起的感染的药物。大多数抗生素是天然产物，其中许多抗生素最初来自土壤细菌（称为放线菌）。尽管在过去40年左右的时间里，抗生素总体上是非常成功的，但近年来出现了耐抗生素细菌（所谓的“超级细菌”）。其中包括MRSA（耐甲氧西林金黄色葡萄球菌）和艰难梭菌，它们引起了人们的极大关注，特别是在英国的医院。不幸的是，市场上的新抗生素越来越少，这增加了未来无法治愈的细菌疾病的前景。西莫环酮D8是一种最近发现的抗生素，目前尚未在临床使用。我们已经能够证明它通过一种新机制靶向细菌中的一种酶（DNA回转酶）。我们的目标是详细了解这种作用机制，以便揭示适用于其他系统的药物-靶标相互作用原理。我们预计，这些知识将提供将被使用的信息，特别是在制药行业，在设计更有效，更特异性的抗生素时，将避免我们目前遇到的耐药性问题。

Antibiotics are drugs used to treat infections caused by bacteria. Most antibiotics are natural products and many of these are derived originally from soil bacteria (called Actinomycetes). Although antibiotics have generally been very successful over the last 40 years or so, recent years have seen the emergence of antibiotic-resistant bacteria (the so-called 'Superbugs'). These include MRSA (methicillin-resistant Staphylococcus aureus) and C. difficule, which have led to significant concern, particularly in UK hospitals. Unfortunately fewer new antibiotics are coming on the market, raising the prospect of untreatable bacteria diseases in the future. Simocyclinone D8 is a relatively recently discovered antibiotic that is not currently in clinical use. We have been able to show that it targets an enzyme in bacteria (DNA gyrase) by a novel mechanism. We aim to understand this mechanism of action in detail in order to reveal principles of drug-target interaction that will be applicable to other systems. We anticipate that this knowledge will provide information that will be used, particularly in the pharmaceutical industry, in the design of more-potent, more-specific antibiotics that will avoid the resistance problems that we are currently encountering.