Validating a drug resistance marker for a globally important ruminant parasite

验证全球重要的反刍动物寄生虫的耐药性标记

• 批准号: NE/X006875/1
• 负责人: Paul McVeigh
• 金额: $ 1.37万
• 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: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FX006875%2F1
• 关键词: Validating; drug; resistance; marker; globally

BBSRC : Christopher Wray : BB/T008776/1Parasitic worm infections are an extremely common issue on livestock farms worldwide, costing farmers and economies billions in production losses. One particularly important species is the barber pole worm, named for its distinctive red and white spiral pattern similar to those seen outside a barbershop. Adult parasites live in an animal's gut, releasing thousands of eggs daily, feeding on the blood of the host. Eggs hatch to larval worms on pasture, and are ingested by another host animal, normally sheep, goat or cattle, spreading the infection. Symptoms of infection include anemia, fluid buildup, reduced growth/milk production and sudden death. Infection is difficult to diagnose before the appearance of these symptoms, with sudden death often the first sign. Thus, farmers periodically apply chemical treatments when concerned about barber-pole worm. This selects for drug-resistant worms; barber-pole worm populations have quickly developed resistance to all of the drugs to which they have been exposed, often with a few years of a new drug's introduction. Thus, monitoring drug-resistance in worm populations (on different farms) is vitally important. Currently, this is done by counting the number of eggs in faeces before and after treatment, with the expectation being that if the worm is susceptible to the drug, there will be fewer eggs present after treatment while in resistant parasites, the number of eggs will remain stable. This technique is unfortunately unreliable due to inconsistent egg numbers being counted in samples, differences in number of eggs counted based on the analyst doing the counting, and a number of other confounding factors. Thus, novel methods for monitoring drug susceptibility are needed. Recent work has identified a genetic mutation within the worm that may be linked to resistance to levamisole, one of the most commonly used drugs against the barber pole worm. In this project, we will compare how common this mutation is between two different worm populations - one which has been exposed to levamisole, and one which has not. We hypothesize that the mutation will be significantly more common in the worm populations that have been regularly exposed to levamisole and so this work will validate this mutation as a marker of resistance to levamisole. This will lead to the development of a test that could be used directly on farms to test for the presence of this mutation. If the test is positive, farmers will know they need to use different drugs. Without this kind of testing, farmers cannot know if the parasite populations on their farms are drug-resistant and thus will continue to apply these drugs, wasting money on drugs that will not improve the health of their animals.

BBSRC: Christopher Wray: BB/ t008776 /1寄生虫感染是世界范围内牲畜养殖场的一个极其普遍的问题，给农民和经济造成数十亿美元的生产损失。其中一个特别重要的物种是理发师杆虫，因其独特的红白螺旋图案而得名，类似于理发店外看到的那些。成年寄生虫生活在动物的肠道中，每天释放数千个卵，以宿主的血液为食。虫卵在牧场上孵化成幼虫，并被另一宿主动物（通常是绵羊、山羊或牛）摄入，从而传播感染。感染症状包括贫血、体液积聚、生长/产奶量减少和猝死。在出现这些症状之前很难诊断感染，而猝死往往是第一个征兆。因此，当担心杆状蠕虫时，农民会定期进行化学处理。这选择了耐药蠕虫；杆状蠕虫种群对它们接触过的所有药物都迅速产生了耐药性，通常需要几年的时间来引入一种新药。因此，监测（不同农场）蠕虫种群的耐药性至关重要。目前，这是通过计算治疗前后粪便中的卵的数量来实现的，预期如果蠕虫对药物敏感，则治疗后出现的卵将减少，而在耐药寄生虫中，卵的数量将保持稳定。不幸的是，由于样品中计数的鸡蛋数量不一致，基于分析人员计数的鸡蛋数量不同，以及许多其他混杂因素，这种技术不可靠。因此，需要新的药物敏感性监测方法。最近的研究发现，这种蠕虫体内的一种基因突变可能与对左旋咪唑的耐药性有关，左旋咪唑是对付理发杆蠕虫最常用的药物之一。在这个项目中，我们将比较这种突变在两种不同的蠕虫种群之间的常见程度——一种接触过左旋咪唑，另一种没有。我们假设这种突变在经常接触左旋咪唑的蠕虫种群中更为常见，因此这项工作将证实这种突变是对左旋咪唑耐药的标志。这将导致一种测试的发展，这种测试可以直接用于农场来测试这种突变的存在。如果检测结果呈阳性，农民就会知道他们需要使用不同的药物。如果没有这种测试，农民就无法知道他们农场上的寄生虫种群是否具有耐药性，因此将继续使用这些药物，浪费金钱在不能改善动物健康的药物上。