Combatting antimicrobial resistance in bovine mastitis through alternative non-antibiotic strategies

通过替代非抗生素策略对抗牛乳腺炎的抗菌药物耐药性

• 批准号: BB/X012778/1
• 负责人: Sharon Huws
• 金额: $ 19.26万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX012778%2F1
• 关键词: Combatting; antimicrobial; resistance; bovine; mastitis

Milk is increasingly in global demand because it is a nutritious natural food that can be processed into many different products accessible to a wide population, It accounted for 16.4% of total agricultural output in the UK in 2020 and was worth £4.4bn in market prices making the UK the thirteenth-largest milk producer in the world. However, this supply of this important safe food source is under threat due to antimicrobial resistant bacteria that infect the udder of dairy cows, causing mastitis. Mastitis is an inflammation of the udder caused by microbial infections that compromise milk production, quality and safety. It is the foremost endemic infectious disease which remains a major challenge to the UK, Canada and global dairy industries. Mastitis has a high prevalence and incidence (~35 (UK) and 19 (Canada) cases /per 100/year). Furthermore, clinical management of mastitis is challenging because not just one but the multiple microorganisms are involved in the infection, making it difficult to diagnose. This is further compounded by the fact that many of these microorganisms that cause mastitis no longer respond to current available antibiotic treatments as they have become resistant to these antibiotics. Antimicrobial resistance (AMR) is closely linked to antimicrobial use and is a major global threat to human health, with projections that it could lead to 5 million human deaths per year. From a public health perspective, AMR in dairy cattle can jeopardize human health, due to the potential spread of mastitic AMR pathogens to humans via consumption of infected dairy products, indirectly when dairy products are disposed of in the environment, or through direct contact with the animals.AMR bacteria in mastitis infections not only poses a challenge for clinical management of mastitis but poses a threat to UK, Canada and global food security. Antimicrobial residues in milk after treatment also contribute to losses from milk discarded during treatment and from withdrawal period post-treatment. Therefore, alternate, new antibiotic-free treatments are urgently needed to fight AMR in dairy cattle. Consequently, it is paramount that we intensify research to enhance our knowledge about the prevalence of AMR determinants involved in the survival and persistence of mastitis isolates. This is vital for clinical management of the disease and for the development of alternative antibiotic-free treatments.Over the past 8 years, we have developed and characterised many novel and efficacious antimicrobial peptides (AMPs). Consequently, in this project, we will evaluate the activity of these new, non-toxic AMPs, which have proven antimicrobial and antibiofilm activity against species of multi-drug resistant (MDR) mastitis bacteria.Additionally, we will assess how treatment of clinical mastitis with these AMP formulations influence the presence and spread of AMR bacteria in dairy cattle. We will also investigate what the microbial and AMR composition of 'normal'/healthy milk versus mastitis milk and evaluate how this changes post treatment with AMPs.This project is timely as mastitis has been highlighted as a key focus by UK Government. The economic, environmental, and social needs to reduce mastitis in dairy herds require effective, targeted treatments for improved management, and the output from this proposed project will facilitate UK Government goal to combat the AMR challenge.

全球对牛奶的需求越来越大，因为它是一种营养丰富的天然食品，可以加工成许多不同的产品，可供广大人口使用。2020年，牛奶占英国农业总产量的16.4%，按市场价格计算价值44亿GB，使英国成为世界第13大牛奶生产国。然而，这种重要的安全食品来源的供应正受到威胁，因为抗菌素耐药性细菌感染奶牛的乳房，导致乳房炎。乳房炎是由微生物感染引起的乳房炎症，影响牛奶产量、质量和安全。它是最重要的地方性传染病，仍然是英国、加拿大和全球乳制品行业面临的主要挑战。乳房炎的患病率和发病率很高(大约35例(英国)和19例(加拿大)/100例/年)。此外，乳房炎的临床管理是具有挑战性的，因为感染涉及的不只是一种微生物，而是多种微生物，这使得诊断变得困难。造成乳房炎的许多微生物对目前可用的抗生素治疗不再有效，因为它们已经对这些抗生素产生了抗药性，这一事实进一步加剧了这一情况。抗菌素耐药性(AMR)与抗菌素的使用密切相关，是对人类健康的重大全球威胁，预计每年可能导致500万人死亡。从公共卫生的角度来看，奶牛的AMR可以危害人类健康，因为乳房性AMR病原体可能通过食用受感染的乳制品、当乳制品被处置在环境中时间接传播给人类，或者通过与动物的直接接触传播。乳房炎感染中的AMR细菌不仅对乳房炎的临床治疗构成挑战，而且对英国、加拿大和全球食品安全构成威胁。处理后牛奶中的抗菌剂残留也会造成处理期间丢弃的牛奶和处理后退出阶段的牛奶损失。因此，迫切需要替代的、不含抗生素的新疗法来对抗奶牛的AMR。因此，至关重要的是，我们必须加强研究，以提高我们对AMR决定因素的流行率的了解，这些决定因素与乳房炎分离株的生存和持久性有关。这对于疾病的临床治疗和非抗生素替代疗法的发展至关重要。在过去的8年里，我们已经开发并鉴定了许多新的和有效的抗菌肽(AMPs)。因此，在这个项目中，我们将评估这些新的、无毒的AMP的活性，这些AMP已经被证明对多种耐药(MDR)乳房炎细菌具有抗菌和抗生物膜活性。此外，我们还将评估这些AMP制剂治疗临床乳房炎如何影响AMR细菌在奶牛中的存在和传播。我们还将调查“正常”/健康牛奶和乳房炎牛奶的微生物和AMR组成，并评估这如何改变AMP治疗后的情况。这个项目是及时的，因为乳房炎已经被英国政府强调为一个关键的重点。减少奶牛群乳房炎的经济、环境和社会需求需要有效、有针对性的治疗，以改善管理，该拟议项目的成果将有助于英国政府实现抗击AMR挑战的目标。