...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes
【24h】

Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes

机译：Aquaglyceroporin 2控制非洲锥虫对美拉索洛和喷他idine的敏感性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance is common and melarsoprol-resistant trypanosomes often display cross-resistance to pentamidine. Although melarso-prol/pentamidine cross-resistance (MPXR) has been an area of intense interest for several decades, our understanding of the underlying mechanisms remains incomplete. Recently, a locus encoding two closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-function screen. Here, we show that AQP2 has an unconventional "selectivity filter." AQP2-specific gene knockout generated MPXR trypanosomes but did not affect resistance to a lipophilic arsenical, whereas recombi-nant AQP2 reversed MPXR in cells lacking, native AQP2 and AQP3. AQP2 was also shown to be disrupted in a laboratory-selected MPXR strain. Both AQP2 and AQP3 gained access to the surface plasma membrane in insect life-cycle-stage trypanosomes but, remarkably, AQP2 was specifically restricted to the flagellar pocket in the bloodstream stage. We conclude that the unconventional aquaglyceroporin, AQP2, renders cells sensitive to both melarsoprol and pentamidine and that loss of AQP2 function could explain cases of innate and acquired MPXR.
机译：非洲锥虫会引起人类昏睡病，这种疾病如果不加化疗，通常会致命。不幸的是，耐药是常见的，耐美索罗尔的锥虫通常对喷他idine有交叉耐药性。尽管美拉索洛尔/戊am交叉耐药性（MPXR）几十年来一直是引起人们极大关注的领域，但我们对潜在机制的理解仍然不完整。最近，在高通量功能丧失筛选中，编码两个密切相关的水甘油糖蛋白AQP2和AQP3的基因座与MPXR相关。在这里，我们显示AQP2具有非常规的“选择性过滤器”。 AQP2特异性基因敲除产生MPXR锥虫体，但不影响对亲脂性砷的抗性，而重组AQP2逆转缺乏天然AQP2和AQP3的细胞中的MPXR。还显示AQP2在实验室选择的MPXR菌株中被破坏。在昆虫生命周期阶段的锥虫中，AQP2和AQP3都可以进入表面质膜，但值得注意的是，在血液阶段，AQP2被专门限制在鞭毛袋中。我们得出的结论是，非常规的水甘油糖蛋白AQP2使细胞对美拉莫尔和喷他idine都敏感，并且AQP2功能的丧失可以解释先天性和获得性MPXR的病例。

著录项

  • 来源
  • 作者

    Nicola Baker; Lucy Glover; Jane C. Munday; David Aguinaga Andres; Michael P. Barrett; Harry P. de Koning; David Horn;

  • 作者单位

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;

    College of Medical,Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom;

    College of Medical,Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom;

    College of Medical,Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom;

    College of Medical,Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom;

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    aquaporin; major instrinsic proteins; transporter; trypanosoma brucei; trypanosomiasis;

    机译：水通道蛋白主要的内在蛋白;运输者布鲁氏锥虫锥虫病;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号