Janssen Saskia, Jayachandran Rajesh, Khathi Lulama, Zinsstag Jakob, Grobusch Martin P, Pieters Jean
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Drug Des Devel Ther. 2012;6:217-24. doi: 10.2147/DDDT.S34006. Epub 2012 Sep 7.
Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteria.
结核病仍然是一种对全球公共卫生有巨大影响的疾病。随着耐药结核病疫情的不断增加，迫切需要新的药物。然而，即使是治疗敏感结核病，也需要新药来缩短治疗时间，从而防止耐药性的产生。在过去十年中，结核病药物研究取得了重大进展，产生了大量目前正在研发中的抗分枝杆菌化合物。在此，我们讨论一些这些有前景的新型结核病药物，以及发现了两个新的潜在药物靶点，用于开发新型有效药物以遏制结核病流行，即冠蛋白1和蛋白激酶G途径。蛋白激酶G由分枝杆菌分泌，负责阻断巨噬细胞内的溶酶体传递。冠蛋白1负责激活磷酸酶钙调神经磷酸酶，从而防止巨噬细胞内吞噬体-溶酶体融合。阻断这两条途径可能导致分枝杆菌的快速杀灭。
