Defining E. coli Diversity in Complex Samples: Methods for Surveillance & Transmission

大肠杆菌是一种普遍存在的细菌，通常由人类携带无害。然而，大肠杆菌也可能引起严重感染，并因对抗生素产生耐药性而复杂化。引起感染的第一步是细菌在个体的肠道中定居。要做到这一点，它们必须被吞下。目前尚不清楚哪些地方最容易获得更危险和/或耐药的大肠杆菌，但通常是由于医院或社区缺乏功能性卫生基础设施而导致个人卫生崩溃。预计设计良好的干预措施可以阻断大肠杆菌的传播，从而减少感染，减少抗生素的使用。由于预防这些细菌传播的潜在干预措施的复杂性和费用，提高对大肠杆菌在何处以及如何获得的了解至关重要。证明一个人从特定来源感染了大肠杆菌，需要从两个流行病学上相关的样本中确认难以区分的大肠杆菌。在复杂样品中区分同一物种的细菌是非常具有挑战性的，目前还没有金标准方法来描述大规模样品中大肠杆菌的物种内多样性。我们将开发基因组学方法，用于大规模准确识别复杂样品中大肠杆菌的多样性和丰度，可用于传播建模。随后，我们将调查其对来自不同国家的不同样本的适用性，以创建不同环境下大肠杆菌多样性目录。

Escherichia coli is a ubiquitous bacteria that is ordinarily harmlessly carried by humans. E. coli can also, however, cause serious infection and be complicated by resistance to antibiotics. The first step in causing infection is for the bacteria to colonise the gut of individuals. For this to happen they must be swallowed. Where more dangerous and/or drug-resistant E. coli are acquired most commonly is not clear, but follows a breakdown in personal hygiene often due to a lack of functional hygiene infrastructure whether in hospitals or the community. It is anticipated that well-designed interventions to interrupt E. coli transmission will lead to fewer infections and less antibiotics being used. Due to the complexity and expense of potential interventions to prevent transmission of these bacteria, an improved understanding of where and how E. coli are acquired is critical.Demonstrating a person has acquired an E. coli from a specific source requires confirmation of indistinguishable E. coli from two epidemiologically connected samples. Distinguishing bacteria of the same species in complex samples is very challenging and there is currently no gold standard approach to describing the within-species diversity of E. coli in a sample at scale. We will develop genomic methods for accurately identifying the diversity and abundance of E. coli in complex samples at scale that can be used for transmission modelling. Subsequently, we will investigate its applicability to diverse samples from different countries to create a catalogue of E. coli diversity in different settings.