Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, Van Voorhis W C, Lukehart S A
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
J Exp Med. 1999 Feb 15;189(4):647-56. doi: 10.1084/jem.189.4.647.
We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity during syphilis infection.
我们使用两种不同的方法，即消减杂交和梅毒基因组文库的差异免疫筛选，鉴定出了一个基因家族，该家族编码梅毒亚种苍白密螺旋体中调理素抗体的靶标和保护性免疫的靶标。两种方法均导致鉴定出一个多态性多拷贝基因家族，该家族与齿垢密螺旋体的主要鞘蛋白具有预测的氨基酸同源性。这个基因家族的一个成员tpr K编码一种蛋白质，该蛋白质预计具有可裂解的信号肽，并位于细菌的外膜中。对苍白密螺旋体的逆转录聚合酶链反应分析表明，Tpr K在苍白密螺旋体的Nichols菌株中优先转录。针对纯化的Tpr K重组可变域的抗体可以调理苍白密螺旋体Nichols菌株以供吞噬，支持了该蛋白质的这一部分暴露于密螺旋体表面的假说。用纯化的Tpr K重组可变域免疫兔子可提供针对苍白密螺旋体Nichols菌株感染的显著保护。该基因家族被认为是梅毒感染期间发病机制和免疫的核心。
