Development, evaluation and translation of next-generation sequencing tools to track MRSA transmission pathways

一种叫做金黄色葡萄球菌的细菌通常是我们正常身体菌群的一部分，对大多数人来说是无害的，但有时可能会引起严重程度不等的感染，从轻微（例如煮沸）到严重（例如心脏瓣膜或骨骼感染）。金黄色葡萄球菌也是人们因感染以外的原因入院后发生感染的主要原因。一些金黄色葡萄球菌菌株对抗生素（甲氧西林）产生了耐药性，而这种抗生素是由金黄色葡萄球菌引起的感染的首选治疗方法。这些耐甲氧西林金黄色葡萄球菌（MRSA）最常见于医院环境。成为耐甲氧西林金黄色葡萄球菌的携带者是感染的先兆，在一个特定的病人身上，在另一个病人身上传播了这种有机体之后，就会出现携带者的发展。医院感染控制旨在防止这些细菌的传播，但有时会失败。揭示细菌如何传播和确定需要加强预防策略的一种方法是进行细菌分型，以确定影响两个患者的MRSA是高度相关（表明它从一个人传播到另一个人）还是不同。然而，这并不简单，因为两种特定的MRSA菌株已经非常成功，它们几乎总是罪魁祸首（它们被称为EMRSA-15和EMRSA-16）。携带或感染其中一种毒株的两名患者可能是相互获得的，也可能是相互独立获得的，目前的实验室分型工具无法区分这两种情况。我们相信，现在有可能开发出新一代的分型工具，根据细菌基因组中单字母DNA变化的识别来区分两种菌株。我们研究的目的是集中在MRSA菌株是重要的在英国。我们将对从全国各地获得的EMRSA-15和-16分离株进行全基因组测序。将对产生的数据进行检查，以确定那些遗传差异，这些差异将被证明对确定群体内的集群最有用。这将为新一代分型技术的发展奠定基础，我们的目标是将其转化为临床环境，在那里它将提供研究MRSA传播在英国和其他地区传播的能力，这种方式以前被证明是不可能的。

A bacterium called Staphylococcus aureus is often part of our normal body flora and is harmless for the majority of people, but may sometimes cause infection that ranges in severity from trivial (e.g. boils) to severe (e.g. infection of the heart valves or bones). Staphylococcus aureus is also the leading cause of infections that occur in people after admission to hospital for reasons other than infection. Some strains of Staphylococcus aureus have acquired resistance to an antibiotic (methicillin) that is otherwise the treatment of choice for infection caused by this organism. These methicillin-resistant Staphylococcus aureus (MRSA) are most often found in the hospital setting. Becoming a carrier of MRSA is the forerunner to infection, and development of carriage in a given patient occurs after transmission of the organism from another patient. Hospital infection control aims to prevent spread of these bacteria but can sometimes fail. One way to reveal how bacteria spread and pinpoint where preventive strategies require strengthening is to perform bacterial typing to determine if MRSA affecting two patients are highly related (suggesting that it passed from one person to another) or different. However, this is not straightforward since two particular strains of MRSA have become so successful that they are almost always the culprits (they are called EMRSA-15 and EMRSA-16). Two patients carrying or infected with one of these strains could have acquired it from each other or may have acquired it independently of each other, and current laboratory typing tools are unable to tell the two situations apart. We believe that it is now possible to develop a new generation of typing tools that distinguish between two strains based on the identification of single letter DNA changes in the bacterial genome. The objective of our study is to focus on MRSA strains that are important in the UK. We will undertake whole genome sequencing of numerous isolates each of EMRSA-15 and -16 obtained from across the country. The data generated will be examined to define those genetic differences that would prove most useful for defining clusters within the group. This will form the basis for the development of a new generation of typing technique that we aim to translate into the clinical setting where it will provide the capability to study the spread of MRSA transmission in the UK and beyond in such a way that has previously proved impossible.