Wiese M, Görcke I
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Germany.
Med Microbiol Immunol. 2001 Nov;190(1-2):19-22. doi: 10.1007/s004300100072.
LMPK, a mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana, is essential for the proliferation of the amastigote, the mammalian stage of the protozoan parasite. This has been demonstrated using deletion mutant promastigotes, the insect stage of the parasite: first, in vitro after differentiation to amastigotes, which subsequently lost their potential to proliferate; second, by infection of peritoneal macrophages, which were able to cope with the infection and cleared the parasites; third, by infection of BALB/c mice, which showed no lesion development. The lmpk deletion mutant promastigotes are a potential live vaccine because they infect macrophages, transform to amastigotes and deliver amastigote antigens to raise an immune response without causing the disease. In addition, inhibition of LMPK in a wild-type infection is likely to resolve the disease and as such, is an ideal target for drug development against leishmaniasis. Here we investigated the presence and copy number of lmpk homologues in Leishmania amazonensis, L. major, L. tropica, L. aethiopica, L. donovani, L. infantum, and L. braziliensis and discuss the results with regard to drug development and vaccination using kinase deletion mutants.
LMPK是墨西哥利什曼原虫的一种丝裂原活化蛋白(MAP)激酶同源物,对于该原生动物寄生虫的哺乳动物阶段——无鞭毛体的增殖至关重要。这已通过使用缺失突变型前鞭毛体(该寄生虫的昆虫阶段)得以证明:首先,在体外分化为无鞭毛体后,这些无鞭毛体随后失去了增殖能力;其次,通过感染腹膜巨噬细胞,腹膜巨噬细胞能够应对感染并清除寄生虫;第三,通过感染BALB/c小鼠,小鼠未出现病变发展。lmpk缺失突变型前鞭毛体是一种潜在的活疫苗,因为它们能感染巨噬细胞,转化为无鞭毛体并递送无鞭毛体抗原以引发免疫反应而不导致疾病。此外,在野生型感染中抑制LMPK可能会治愈疾病,因此,它是抗利什曼病药物开发的理想靶点。在此,我们研究了亚马逊利什曼原虫、硕大利什曼原虫、热带利什曼原虫、埃塞俄比亚利什曼原虫、杜氏利什曼原虫、婴儿利什曼原虫和巴西利什曼原虫中lmpk同源物的存在情况和拷贝数,并就使用激酶缺失突变体进行药物开发和疫苗接种的结果进行了讨论。