Johnson P J, Schuck B L, Delgadillo M G
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024-1747.
Mol Biochem Parasitol. 1994 Jul;66(1):127-37. doi: 10.1016/0166-6851(94)90043-4.
We have characterized a gene encoding an Adenosine triphosphate (ATP) Binding Cassette (ABC) transmembrane protein from Trichomonas vaginalis, an early-diverging protozoan parasite. This gene, Tvpgp1, encodes a 589-amino acid protein with an amino-terminal hydrophobic region, 6 potential membrane-spanning segments and a carboxy-terminal ATP binding site. Tvpgp1 is most similar in sequence to mammalian P-glycoproteins, 170 kDa transport proteins which are frequently overexpressed in multiple drug-resistant (Mdr) tumor cell lines. However, Tvpgp1 is half the size of typical P-glycoproteins which are tandem duplications. These data suggest that the duplication/fusion events which gave rise to the bipartite structure comprised of 2 similar halves which characterize eukaryotic P-glycoproteins may have occurred after the divergence of trichomonads (Parabasalia) from the main line of eukaryotic evolutionary descent. We have examined 7 metronidazole resistant strains of T. vaginalis to determine whether the Tvpgp1 gene is overexpressed or amplified. 2 drug resistant strains show a 2-3-fold overexpression and one shows a 20-fold overexpression of Tvpgp mRNA. The gene is not amplified in any of the drug resistant strains. On the contrary, 4 of the 7 resistant strains lack one of 2 Tvpgp genes found in drug-sensitive strains.
我们已经鉴定了一个来自阴道毛滴虫（一种早期分化的原生动物寄生虫）的编码三磷酸腺苷（ATP）结合盒（ABC）跨膜蛋白的基因。这个基因，Tvpgp1，编码一个589个氨基酸的蛋白质，该蛋白质具有一个氨基末端疏水区域、6个潜在的跨膜片段和一个羧基末端ATP结合位点。Tvpgp1在序列上与哺乳动物P-糖蛋白最为相似，P-糖蛋白是一种170 kDa的转运蛋白，在多药耐药（Mdr）肿瘤细胞系中经常过度表达。然而，Tvpgp1的大小只有典型P-糖蛋白（串联重复）的一半。这些数据表明，导致真核生物P-糖蛋白特征性的由两个相似部分组成的二分结构的复制/融合事件可能发生在滴虫（副基体门）从真核生物进化主线分化之后。我们检测了7株甲硝唑耐药的阴道毛滴虫菌株，以确定Tvpgp1基因是否过度表达或扩增。2株耐药菌株显示Tvpgp mRNA有2至3倍的过度表达，1株显示有20倍的过度表达。该基因在任何耐药菌株中均未扩增。相反，7株耐药菌株中有4株缺少在药物敏感菌株中发现的2个Tvpgp基因中的一个。
