MRSA在医疗保健环境中仍然提出了多少问题？
耐甲氧西林的史金黄色葡萄球菌（MRSA）是一个成功的克隆的波浪，随后被其他人取代。MRSA由于人口的潮起潮落而构成了持续的威胁。
Although the situation in the UK has greatly improved since 2004, MRSA remains a major scourge in healthcare settings globally. In Singapore, the organism is the most common antimicrobial-resistant bacterium causing nosocomial infections, with more than 3,000 infections logged each year in a population of 5 million.
正如我们的研究所表明的那样，疾病的负担是由成功地适应医院环境生存和繁荣的成功克隆引起的。这意味着他们特别顽强且难以消除，因此对弱势患者构成了不断的威胁。
除了MRSA在医疗环境中提出的问题外，近年来，MRSA的流行克隆引起了社区疾病，还可以扩散到医院。这证明了我们认为是医疗保健和社区感染之间的模糊界限，也证明了MRSA作为人类病原体的适应性。
您为什么在这项特定研究中专注于新加坡？
This study reflects the combined interests of the groups in the UK and Singapore of gaining a greater understanding of this success of MRSA, and improving the ways in which to combat it.
这次合作的种子是由一个休假播种的，该休假带来了从新加坡的传染病医生李Yang Hsu博士，到剑桥的惠康信托基金会，与病原体基因组学集团的马特·霍顿（Matt Holden）一起工作，并获得了生物信息学的经验。和整个基因组测序。
…the succession of MRSA in Singapore provided a unique opportunity to look at two clones going head-to-head in a healthcare system.
以前，整个基因组测序在研究细菌病原体的出现和演变中的应用倾向于集中在单个克隆上，因此，新加坡MRSA的连续系统。
在许多方面，新加坡被证明是研究MRSA进化成功的理想研究地点。新加坡是一个与公共医院紧密相互联系的小国，其中一个较旧的MRSA克隆人迅速失去了其“垄断”，将其“垄断”转换为一个起源于英国的较新的大流行MRSA克隆。
从30年的这项工作中获得样品有多困难？
由于临床实验室空间在人口稠密的新加坡的溢价中，这是当地实验室在规定的一段时间后丢弃所有临床细菌分离株的做法，除非将这些分离株保留用于临时研究或其他项目。在这项研究中，我们很幸运的是，当地医院从2000年代开始保持隔离，这主要是由于当地临床医生的努力，他们对MRSA日益增长的问题的兴趣确保了保留分离株。
The older isolates proved to be a bigger problem, but here we were again extremely lucky that an older collaboration with Prof Warren Grubb from the Gram-Positive Typing Laboratory at Curtin University, Perth, Australia had resulted in Singaporean isolates from the 1980s and 1990s being stored over there.
您利用贝叶斯技术来研究新加坡MRSA历史，这些优势有什么优势？
In this study we used a series of methods and tools to investigate the genetics and evolutionary relationships of MRSA in Singapore, including some in which Bayesian statistical methods lay at their heart.
使用这些技术，我们能够深入研究整个基因组测序数据，从而对塑造MRSA种群的进化事件有更大的时间了解，从而突出了新加坡MRSA历史上的重要事件。我们还能够使用这些方法来检查竞争MRSA克隆的遗传多样性，并确定人群的显着变化。
最终，贝叶斯技术提供了用于分析整个基因组测序数据的解决方案，这些数据被证明是最有利的。它不仅有助于确定新的MRSA变体的出现，而且还确定了随后的流行病学观察结果支持的数据中的趋势。
您的主要发现之一是抗生素使用在驱动甲氧西林抗性的演变中起着重要作用。有证据表明金黄色葡萄球菌is also becoming resistant to alternative antibiotics?
相反，MRSA的较新的流行克隆变得越来越耐药地对替代性非甲酰胺抗生素的抵抗力。甲氧西林是B-内酰胺抗生素。具有适应性成本的耐药性具有抵抗力，而MRSA的新克隆在这方面的效率更加有效，这是合理的。
In our study, and earlier published works looking at several global MRSA clones, the key antibiotic resistance determinant (other than to b-lactam antibiotics) is to the fluoroquinolone antibiotics, a class of antibiotics that are excreted in sweat and on to the skin. The increase in the use of fluoroquinolones in recent decades has been a key driver of the success of pandemic clones of MRSA that have developed resistance to this antibiotic.
You report that early Singaporean MRSA strains correspond to those seen in the Hungarian epidemic, and that MRSA strains that appeared in Singapore from the year 2000 onwards corresponded to those seen in UK hospitals in the early 1980s. Does this turn the common fear of diseases spreading into the West on its head?
这仅显示了世界的相互联系。顺便说一句，在这项研究中，我们还发现，在2000年代在伦敦一家医院发生爆发的MRSA菌株之一可能起源于新加坡。
A recurring observation from many of the whole genome sequencing studies examining the emergence and spread of bacterial human pathogens is that the pathogen’s population structure is as much a story about humans and their activities, as it is about bacteria.
多年来，MRSA的多个大流行克隆出现了。
对于MRSA而言，是一种殖民皮肤并适应医院生存和壮成长的生物，这尤其明显。多年来，MRSA的多个流血克隆出现了，这些克隆在全球范围内循环，这是由于动态人群的驱动（以及它们的抗生素使用）。在这方面，就传染病的流行病学而言，新加坡占据了精致的地位，这是一个人口稠密的全球枢纽。
What does your study mean for research into MRSA and other pathogen epidemics?
这项研究强调，除了临床实践和抗生素用法外，在医疗保健环境中细菌种群之间的竞争在驱动病原体进化方面具有重要作用。
In particular, it revealed that during clone succession, new variants emerged in a declining clone via horizontal gene transfer, introducing genes that promote survival and persistence. In the case of the MRSA we have studied, the genes in question comprised an arginine catabolic mobile element (ACME), a mobile genetic element that is also found in an epidemic community-associated MRSA (USA300) that has become dominant in the USA.
ACME编码的功能与增强的皮肤定植有关，而MRSA成功的重要方面突出了其与人体上最大器官相互作用的能力。
More generally, our study illustrates the value of examining the success of epidemic clones in a wider context rather than in isolation. This is especially important from a public health point of view. As sequencing technology becomes more widely embraced into pathogen surveillance, we will have the capacity to take a more holistic approach to investigating pathogen population structure. With the right tools and approaches we will be able to use whole genome sequencing to not only monitor present dangers, but to identify where new problems emerge out of previous dangers, and target our interventions accordingly.
您的研究下一步是什么？
The next chapter for this particular work is a collaborative project between Singaporean hospitals, the Wellcome Trust Sanger Institute, and the University of St. Andrews, to examine the transmission of MRSA between acute-care and community hospitals, and also between nursing homes and the hospitals.
更广泛地说，我们未来的研究的目标是将基因组观点转化为对成功医院适应的微生物的生理理解。
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