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

开发、评估和翻译下一代测序工具以追踪 MRSA 传播途径

• 批准号: G1000803/1
• 负责人: Sharon Peacock
• 金额: $ 410.76万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000803%2F1
• 关键词: Development; evaluation; translation; next; generation

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.

金黄色葡萄球菌通常是我们正常体内菌群的一部分，对大多数人来说是无害的，但有时可能会引起严重程度从轻微（例如煮沸）到严重（例如心脏瓣膜或骨骼感染）的感染。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。某些金黄色葡萄球菌菌株已获得对抗生素（甲氧西林）的耐药性，而抗生素是该微生物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) 最常见于医院环境中。成为 MRSA 的携带者是感染的先兆，并且在从另一名患者传播该微生物之后，特定患者中就会出现携带者。医院感染控制旨在防止这些细菌的传播，但有时可能会失败。揭示细菌如何传播并查明需要加强哪些预防策略的一种方法是进行细菌分型，以确定影响两名患者的 MRSA 是否高度相关（表明它从一个人传播到另一个人）或不同。然而，这并不简单，因为两种特殊的 MRSA 菌株已经变得如此成功，以至于它们几乎总是罪魁祸首（它们被称为 EMRSA-15 和 EMRSA-16）。两名携带或感染其中一种菌株的患者可能是从彼此那里获得的，也可能是彼此独立获得的，而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。我们研究的目的是关注在英国重要的 MRSA 菌株。我们将对从全国各地获得的大量 EMRSA-15 和 -16 分离株进行全基因组测序。将检查生成的数据，以确定那些对于定义群体内的聚类最有用的遗传差异。这将成为开发新一代分型技术的基础，我们的目标是将其转化为临床环境，从而提供研究 MRSA 在英国及其他地区传播的能力，而这种方式以前被证明是不可能的。