Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Int J Mol Med. 2012 Jul;30(1):75-84. doi: 10.3892/ijmm.2012.967. Epub 2012 Apr 10.
Orientia tsutsugamushi (O. tsutsugamushi), the causative agent of scrub typhus, is an obligate intracellular pathogen. Recent studies have demonstrated the complete genome of O. tsutsugamushi. However, the route and detailed molecular mechanism for O. tsutsugamushi to get accessed into mammalian cells remains unclear. In this study, we demonstrated different adhesive properties of three major outer membrane proteins of O. tsutsugamushi, TSA56, TSA47 and TSA22. TSA56 showed higher antibody responses against patient serum samples compared with those of TSA47 and TSA22. In the adhesion assay, TSA56 exhibited a relative higher adhesion to host cells than TSA47 and TSA22, suggesting that TSA56 is the major outer membrane protein required for O. tsutsugamushi adhesion. Furthermore, the antigen domain (AD) I (residues 19-114) corresponding to the extracellular domain of TSA56 demonstrated a relative high antibody response against the patients' sera than the previously reported ADIII (residues 237-366), which has been suggested to facilitate the invasion of O. tsutsugamushi through interaction with fibronectin. Taken together, our results consistently showed that TSA56 of O. tsutsugamushi is important in the adhesion of Escherichia coli (E. coli) transformants to Vero cells. Moreover, in contrast to known ADIII-fibronectin interactions, TSA56-ADI may also play a role in the adhesion and/or invasion of O. tsutsugamushi to its host cells through unidentified receptors. A further study aimed at delineating the receptor of TSA56-ADI during O. tsutsugamushi infection is warranted.
恙虫病东方体（Orientia tsutsugamushi）是恙虫病的病原体，是一种必需的细胞内寄生菌。最近的研究已经证明了恙虫病东方体的完整基因组。然而，恙虫病东方体进入哺乳动物细胞的途径和详细的分子机制仍不清楚。在这项研究中，我们证明了恙虫病东方体的三种主要外膜蛋白 TSA56、TSA47 和 TSA22 的不同粘附特性。与 TSA47 和 TSA22 相比，TSA56 对患者血清样本表现出更高的抗体反应。在粘附实验中，TSA56 对宿主细胞的粘附性相对高于 TSA47 和 TSA22，表明 TSA56 是恙虫病东方体粘附所必需的主要外膜蛋白。此外，与先前报道的 ADIII（残基 237-366）相比，对应 TSA56 细胞外结构域的抗原结构域 I（残基 19-114）对患者血清的抗体反应相对较高，这表明 ADIII 有助于恙虫病东方体通过与纤维连接蛋白相互作用侵入宿主细胞。综上所述，我们的研究结果一致表明，恙虫病东方体的 TSA56 在外膜蛋白转化大肠杆菌（E. coli）与 Vero 细胞的粘附过程中起重要作用。此外，与已知的 ADIII-纤维连接蛋白相互作用不同，TSA56-ADI 也可能通过未鉴定的受体在恙虫病东方体与宿主细胞的粘附和/或入侵中发挥作用。进一步研究旨在阐明 TSA56-ADI 在恙虫病东方体感染过程中的受体。
