The pH of the malaria parasite's digestive vacuole and its role in antimalarial drug resistance

疟疾寄生虫消化液泡的pH值及其在抗疟药物耐药性中的作用

• 批准号: nhmrc : 179804
• 负责人: Prof Kiaran Kirk
• 金额: $ 14.07万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/ph-malaria-parasites-drug-resistance/81188
• 关键词: pH; malaria; parasite; digestive; vacuole

Malaria is an infectious disease that infects an estimated 300-500 million people and kills an estimated 1.5-2.7 million people annually. The microscopic parasite responsible for the disease is becoming increasingly resistant to most of the antimalarial drugs presently available. However the mechanisms by which it does so are very poorly understood. The malaria parasite invades the red blood cells of its victim. Once itside, it sets about consuming the contents of the cell, ingesting them and depositing them in a small acidic compartment called the digestive vacuole. Many of the antimalarial drugs presently in use target this compartment and interfere with the processes going on inside it. There is evidence that resistance to antimalarial drugs arises as a result of changes in this compartment, though what these changes are, and how they occur remains a mystery. This work focuses on the mechanisms involved in controlling the acidity of the parasite's digestive vacuole. We have preliminary evidence that parasites showing different levels of antimalarial drug resistance have different levels of acidity in their vacuoles, and that this may be due to differences in the rate at which acid leaks from this compartment. The aim of this work is to obtain a detailed understanding on the mechanisms by which the acidity of the parasite's digestive vacuole is regulated and to gain some insight into whether and how these mechanisms might differ between drug-resistant and drug-sensitive parasites. By so doing, this work might be expected, in the long term, to provide a basis for the devolpment of new drugs with which to combat this deadly and increasingly threatening disease.

疟疾是一种传染病，估计每年感染3亿至5亿人，并导致约150万至270万人死亡。导致这种疾病的微小寄生虫对现有的大多数抗疟疾药物正变得越来越耐药。然而，人们对它实现这一目标的机制知之甚少。疟疾寄生虫侵入受害者的红细胞。一旦消化完毕，它就会开始消耗细胞中的内容物，将它们摄取并存放在一个名为消化液泡的小酸性隔间中。目前使用的许多抗疟疾药物都针对这个隔室，并干扰其内部进行的过程。有证据表明，对抗疟疾药物的耐药性是由于这种间隔的变化而产生的，尽管这些变化是什么，以及它们是如何发生的仍然是一个谜。这项工作的重点是控制寄生虫消化液泡的酸度的机制。我们有初步证据表明，表现出不同水平的抗疟疾耐药性的寄生虫在其液泡中有不同程度的酸性，这可能是由于从这个隔室泄漏酸的速度不同所致。这项工作的目的是详细了解寄生虫消化液泡酸性的调节机制，并深入了解这些机制是否以及如何在耐药寄生虫和敏感寄生虫之间存在差异。通过这样做，从长远来看，这项工作可能会为开发新的药物提供基础，用来对抗这种致命和日益危险的疾病。