'See and Sequence' - Genomic surveillance of antimicrobial resistant and high-risk pathogenic clones within the Philippines

病原菌种类的抗菌素耐药性日益增加的幽灵每天都在扩大。现有的监测网络需要新的工具，以更丰富、更详细地了解一个地区AMR在何时何地发生。这将有助于公共卫生，并导致更好的病人护理和预防传播。然而，公共卫生微生物学家在处理致病微生物物种时面临着重大挑战，这些挑战可以概括为：1）识别高风险谱系-即可能导致疾病的人群中的危险亚型。谱系对什么抗生素有抗性，有多大可能引起疾病，有多容易传播给他人）。3）感染控制。- 利用这些信息制定治疗和预防传播的策略。细菌物种的全基因组测序（WGS）为我们提供了寻找耐药性和毒力基因组特征的手段（即如果存在的话，给我们一些指示，什么药物可以用来治疗个人），但也为我们提供了识别传播的方法-例如，通过建立“家谱”来表明哪些基因组与其他基因组更相似。此外，由于数据的数字性质，基因组序列和相关的元数据可以通过互联网存储和访问，从而为区域，国家和国际比较提供了可能。我们打算在菲律宾的国家抗菌素监测网络中使用WGS，以将分辨率的提高引入国家网络。首先，我们将在参考实验室中安装本地测序能力，并与WGS用于公共卫生的世界领导者Wellcome Trust桑格研究所合作，将在整个项目中提供WGS使用的培训和能力建设。其次，我们将对过去几年在菲律宾流行的一组有代表性的历史菌株进行测序，以提供一个“参考数据库”，从而开始积极的监测。最后，我们将利用当前的微生物学来“标记”具有不寻常抗生素耐药性的菌株，开始一个前瞻性测序过程，并将同期数据与参考数据库进行比较。至关重要的是，这也将使来自菲律宾的数据与来自世界其他地区的数据进行比较，不仅有助于识别进出该地区的潜在传播，而且有助于作为全球抗生素耐药性监测的一部分。该项目使菲律宾处于分子流行病学的前沿。

The spectre of increasing antimicrobial resistance in pathogenic bacterial species looms larger each day. Currnetly existing surveillance networks need new tools to enable richer and more detailed understanding of where and when AMR is arising across a region. This will aid public health and lead to better patient care and prevention of spread. However, there are significant challenges facing public health microbiologists when tackling pathogenic microbial species which can be broadly summarised as:1) Identification of high-risk lineages - ie dangerous sub-types in a population likely to cause disease.2) Risk assessment following identification (eg., what antibiotics is the lineage resistant to, how likely to cause disease, how easy to transmit to others).3) Infection control. - Using this information to inform strategies in treatment and the prevention of spread.Whole Genome Sequencing (WGS) of bacterial species provides us with the means to look for genomic signatures of resistance and virulence (ie genes that if present, give us some indication as to what drugs could be used to treat the individual) but also provides us with ways of identifying transmission - for example by building 'family trees' indicating which genomes are more similar to others. Furthermore, due to the digital nature of the data, genome sequences and associated metadata can be stored and accessed via the internet opening up the possible for regioinal, national and international comparison. We intend to utilise WGS within the National antimicrobial surveillance network in the Philippines to introduce this increase in resolution to a national network.Firstly, we will install local sequencing capacity in the Reference Laboratory and, in conjunction with The Wellcome Trust Sanger Institute, the world leader in the use of WGS for public health, will provide training and capacity building for the use of WGS throughout the project.Secondly, we will sequence a representative set of historical strains circulating over the preceding years in the Philippines to provide a 'reference database' with which to start active surveillance.Finally, we will, utilising current microbiology to 'flag' isolates with unusual antibiotic resistance, start a process of prospective sequencing and comparison between contempory data and the reference database.Crucially, this will also allow the comparsion of data from the Philippines with data from other parts of the world to aid, not only identification of potential transmissions to/from the Region but to act as part of a global surveillance of antimicrobial resistance. This project places the Philippines at the forefront of molecular epidemiology.