Weaver Kathryn J, May Cassandra J, Ellis Brian L
Department of Biology and Chemistry, Bethel College, Mishawaka, Indiana, United States of America.
PLoS One. 2017 Jun 20;12(6):e0179376. doi: 10.1371/journal.pone.0179376. eCollection 2017.
Soil-transmitted helminths (STHs) are intestinal parasitic nematodes that infect humans, and are transmitted through contaminated soil. These nematodes include the large roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancylostoma ceylanicum, Ancylostoma duodenale, and Necator americanus). Nearly 1.5 billion people (~24% of the population) worldwide are infected with at least one species of these parasites, burdening the poor, in particular, children and pregnant women. To combat these diseases, the WHO only recognizes four anthelmintic drugs, including the preferred drug, albendazole, for mass drug administration (MDA). These four drugs have a total of two different mechanisms of action, and, as expected, resistance has been observed. This problem calls for new drugs with different mechanisms of action. Although there is precedence for the use of Caenorhabditis elegans (C. elegans), a free-living nematode, as a model for drug screening and anthelmintic testing, their usefulness for such anthelmintic study is not clear as past research has shown that C. elegans did not show a strong response to albendazole, the MDA drug of choice, in comparison with various STHs under similar treatment. To further examine if C. elegans has the potential to be a good model organism for anthelmintic drug study, we employed a health rating scale in order to tease out potential effects of albendazole, and other anthelmintics, that may have been missed using a binary, dead/alive scale. Using the health-rating scale we found that although the worms may have not been dying, they were sick, showing dose responses to anthelmintic drugs, including albendazole, reinforcing C. elegans as a useful model for anthelmintic study.
土壤传播的蠕虫(STH)是感染人类的肠道寄生线虫,通过受污染的土壤传播。这些线虫包括大型蛔虫(蛔虫)、鞭虫(鞭虫)和钩虫(锡兰钩虫、十二指肠钩虫和美洲板口线虫)。全球近15亿人(约占人口的24%)感染了这些寄生虫中的至少一种,给穷人,尤其是儿童和孕妇带来了负担。为了对抗这些疾病,世界卫生组织只认可四种驱虫药物,包括首选药物阿苯达唑,用于大规模药物给药(MDA)。这四种药物共有两种不同的作用机制,并且正如预期的那样,已经观察到了耐药性。这个问题需要具有不同作用机制的新药。尽管有将自由生活的线虫秀丽隐杆线虫(C. elegans)用作药物筛选和驱虫测试模型的先例,但它们在这种驱虫研究中的有用性尚不清楚,因为过去的研究表明,与在类似处理下的各种土壤传播的蠕虫相比,秀丽隐杆线虫对MDA的首选药物阿苯达唑没有表现出强烈反应。为了进一步研究秀丽隐杆线虫是否有潜力成为驱虫药物研究的良好模式生物,我们采用了健康评分量表,以梳理出阿苯达唑和其他驱虫药可能被二元的死/活量表遗漏的潜在影响。使用健康评分量表,我们发现,尽管蠕虫可能没有死亡,但它们生病了,对包括阿苯达唑在内的驱虫药表现出剂量反应,这进一步证明秀丽隐杆线虫是驱虫研究的有用模型。