Julius-Maximilians-University Würzburg, Research Center for Infectious Diseases, Josef-Schneider-Strasse 2, Building D15, 97080 Würzburg, Germany.
Curr Mol Med. 2010 Apr;10(3):335-49. doi: 10.2174/156652410791065273.
The impact of selected antibiotics on combating malaria infections was discovered in the mid of last century. Only recently, studies on their modes of action in malaria parasites have been initiated, prompted by the discovery of a prokaryotic organelle, the apicoplast. This plastid-derived structure, which originates from a secondary endosymbiotic event, possesses important metabolic as well as housekeeping functions, including fatty acid and heme biosynthesis. Due to its indispensability for parasite survival it represents a promising target for the use of antibiotics in malaria therapy. Most antibiotics cause a delayed death phenotype, which manifests in the late onset of antimalarial activity during the second replication cycle of the pathogen. This review will describe the effect of classical antibacterial agents against malaria parasites and the use of some of these compounds in clinical settings. Firstly we discuss the current knowledge about the physiological and morphological effects of antibiotics on the parasite and the apicoplast in particular, with special focus on the delayed death effect. Secondly antimalarial antibiotics are specified and their effects in vitro are compared with available in vivo data and clinical studies. Major precautions and side effects are described.
上个世纪中叶发现，某些抗生素对治疗疟疾感染有影响。直到最近，由于发现了一个原核细胞器——质体，对疟原虫中抗生素作用模式的研究才刚刚开始。这个由二次内共生事件产生的质体衍生结构，具有重要的代谢和管家功能，包括脂肪酸和血红素的生物合成。由于它对寄生虫生存的不可或缺性，它代表了在疟疾治疗中使用抗生素的一个有前途的目标。大多数抗生素会导致延迟死亡表型，这种表现在病原体的第二个复制周期中，抗疟活性的晚期开始时出现。这篇综述将描述经典抗菌剂对疟原虫的作用，以及这些化合物在临床环境中的应用。首先，我们讨论了抗生素对寄生虫和质体，特别是对延迟死亡效应的生理和形态影响的现有知识。其次，指定了抗疟抗生素，并将其在体外的作用与现有的体内数据和临床研究进行了比较。描述了主要的预防措施和副作用。
