Validating a drug resistance marker for a globally important ruminant parasite

BBSRC：克里斯托弗·雷：BB/T008776/1寄生虫感染是全球畜牧场的一个极其常见的问题，给农民和经济体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杆蠕虫，因其独特的红色和白色螺旋图案而得名，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蠕虫幼虫，并被另一种宿主动物（通常是绵羊、山羊或牛）摄入，传播感染。感染的症状包括贫血、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，猝死通常是第一个迹象。因此，农民在担心理发杆虫时会定期使用化学治疗。这选择了抗药性蠕虫;理发杆蠕虫种群迅速对它们接触过的所有药物产生了抗药性，通常是在几年内引入一种新药。因此，监测蠕虫种群（不同农场）的耐药性至关重要。目前，这是通过计算治疗前后粪便中的虫卵数量来完成的，预计如果蠕虫对药物敏感，治疗后虫卵会减少，而在耐药寄生虫中，虫卵数量将保持稳定。不幸的是，由于样本中计数的鸡蛋数量不一致，基于进行计数的分析员计数的鸡蛋数量存在差异，以及许多其他混杂因素，这种技术是不可靠的。因此，需要用于监测药物敏感性的新方法。最近的工作已经确定了蠕虫内的基因突变，可能与左旋咪唑的耐药性有关，左旋咪唑是对抗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个不同的蠕虫种群中的普遍程度-一个已经暴露于左旋咪唑，另一个没有。我们假设突变在经常暴露于左旋咪唑的蠕虫种群中更常见，因此这项工作将验证这种突变作为左旋咪唑抗性的标志。这将导致开发一种可以直接用于农场的测试，以测试这种突变的存在。如果测试结果呈阳性，农民将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抗药性，从而继续使用这些药物，浪费金钱购买不会改善动物健康的药物。

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.