Tackling antimicrobial resistance in dairy production: smartphone microfluidics for parallel resistance gene detection alongside functional antibiotic

细菌的抗菌素耐药性（AMR）是人类和动物健康以及食品生产/安全的主要威胁。在食用动物中使用抗生素有助于抗生素耐药菌（ARB）的出现和传播，ARB可以通过各种途径从动物传播到人类，包括污染的牛奶和乳制品进入人类食物链。关于英国消费者在牛奶和其他乳制品（如生奶奶酪）中可能暴露于AMR的其他数据以及相关健康风险的评估至关重要。然而，2016年食品标准局的一份报告证实，英国牛奶和乳制品中AMR的科学证据和监测数据仍然有限。该项目旨在利用智能手机和微流体技术开发用于检测和分析AMR的新一代工具，为理解和控制这种公共卫生风险提供新数据。在我们最近对牛奶样品进行的小规模可行性研究中，我们发现了抗生素耐药细菌的例子，包括致病性和非致病性物种（即益生菌/健康牛奶微生物群）。此外，一些细菌对多种抗生素（>3种不同的类别）具有耐药性，包括“最高优先级至关重要”的抗生素。我们在健康奶牛和患乳腺炎的奶牛的牛奶中发现了这些。携带AMR基因的ARB的存在引起了人们对原料奶以及由原料奶制成的奶酪安全性的担忧。导致乳腺炎感染的ARB也使维持动物健康和福利变得具有挑战性，因为治疗乳腺炎（以及其他感染）变得更具挑战性，治疗失败更常见。目前的AMR检测方法仍然太慢（>2d），并且对于监测和AMR检测来说都太费力，以指导治疗乳腺炎时的抗生素选择，需要集中实验室的专业技术人员。微流体技术可以进行快速测试，当与最新的智能手机和数字成像技术相结合时，这些实验室技术可以被运送到现场。我们将开发尖端的快速和便携式技术，用于并行检测AMR基因和功能性抗生素敏感性。这些将专门针对乳制品生产中的AMR挑战而开发，通过让我们了解和预防牛奶和奶酪生产中出现的AMR并传播给人类，为食品安全做出贡献。

Antimicrobial resistance (AMR) in bacteria is a major threat to human and animal health, and to food production/security. Antimicrobial use in food animals contributes to the emergence and spread of antimicrobial resistant bacteria (ARB), which can spread from animals to humans via various pathways, including contaminated milk and dairy products entering the human food chain. Additional data regarding the potential exposure of British consumers to AMR in milk and other dairy products (e.g. raw milk cheeses) and assessment of associated health risk is vital. However, scientific evidence and surveillance data regarding AMR in milk and dairy products in the UK remains limited, confirmed in a 2016 Food Standards Agency report. This project aims to develop miniaturised, next-generation tools for the detection and analysis of AMR, exploiting smartphone and microfluidic technology, to provide new data for understanding and controlling this public health risk. In our recent small-scale feasibility study of milk samples, we found examples of antibiotic resistant bacteria, both pathogenic and non-pathogenic species (i.e. commensals/healthy milk microbiota). Furthermore, some bacteria were resistant to multiple antibiotics (>3 different classes) including 'Highest Priority Critically Important' antibiotics. We found these in milk from both healthy cows and suffering from mastitis. The presence of ARB carrying AMR genes raises concerns about the safety of raw milk as well as cheese made from raw milk. ARB causing mastitis infection also makes it challenging to maintain animal health and welfare, because treating mastitis (and indeed other infections) becomes more challenging and treatment failure more common. Current AMR detection methods remain far too slow (>2d) and laborious for both surveillance, and for AMR detection to guide antibiotic selection when treating mastitis, requiring expert technicians in centralised labs. Microfluidics can perform rapid tests and when combined with the latest smartphone and digital imaging technology, these laboratory techniques can be transported into the field. We will develop cutting-edge rapid and portable technology for parallel detection of both AMR genes, and of functional antibiotic susceptibility. These will be developed specifically for addressing AMR challenges in dairy production, contributing to food security by allowing us to understand and prevent AMR arising in milk and cheese production and spreading to humans.