Validating a drug resistance marker for a globally important ruminant parasite

BBSRC：Christopher Wray：BB/T008776/1寄生虫感染在世界各地的畜牧场是一个极其常见的问题，给农民和经济造成数十亿美元的生产损失。一个特别重要的物种是理发师杆虫，它的名字是因为它独特的红白相间的螺旋图案，类似于在理发店外看到的那些。成虫生活在动物的肠道中，每天释放数以千计的卵，以宿主的血液为食。卵在牧场孵化成幼虫，然后被另一种宿主动物摄取，通常是绵羊、山羊或牛，从而传播感染。感染的症状包括贫血、液体堆积、生长/产奶量减少和猝死。在这些症状出现之前，感染很难诊断，猝死往往是第一个症状。因此，农民在担心理发杆虫时，会定期进行化学处理。这选择了抗药性蠕虫；理发线虫种群很快就对它们所接触的所有药物产生了抗药性，通常是在一种新药推出几年后。因此，监测(不同农场)蠕虫种群的抗药性至关重要。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，治疗后虫卵将会减少，而在耐药寄生虫中，虫卵数量将保持稳定。不幸的是，这项技术是不可靠的，因为样本中计算的鸡蛋数量不一致，基于进行计数的分析师计算的鸡蛋数量不同，以及许多其他混杂因素。因此，需要新的方法来监测药物敏感性。最近的工作发现了这种蠕虫体内的一种基因突变，这种突变可能与对左旋咪唑的抗药性有关，左旋咪唑是治疗理发杆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群体中的普遍程度-一个已经接触过左旋咪唑，另一个没有。我们假设，这种突变在经常接触左旋咪唑的蠕虫种群中明显更常见，因此这项工作将验证这种突变是左旋咪唑耐药的标志。这将导致开发一种可以直接在农场使用的测试方法，以测试这种突变的存在。如果检测呈阳性，农民将知道他们需要使用不同的药物。如果没有这种检测，农民就无法知道他们农场的寄生虫种群是否具有抗药性，从而将继续使用这些药物，浪费金钱在那些不会改善动物健康的药物上。

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.