Iwashita Hirofumi, Fujii Shigemoto, Kawamura Yoshiaki, Okamoto Tatsuya, Sawa Tomohiro, Masaki Takayuki, Nishizono Akira, Higashi Shuichi, Kitamura Toshio, Tamura Fumio, Sasaki Yutaka, Akaike Takaaki
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Clin Vaccine Immunol. 2008 Mar;15(3):513-21. doi: 10.1128/CVI.00439-07. Epub 2008 Jan 2.
Helicobacter cinaedi infection is now recognized as an increasingly important emerging disease. Its pathogenesis and epidemiological features are not fully understood, however. Here, we investigated the antigenic protein of H. cinaedi and the immunological response to it in H. cinaedi-infected patients. We constructed a genomic library of H. cinaedi from an H. cinaedi clinical isolate, and various H. cinaedi recombinant proteins were expressed. We identified the 30-kDa protein, encoded in an 822-bp H. cinaedi genome, as a major antigen, which was specifically recognized by serum from an H. cinaedi-immunized rabbit and H. cinaedi-infected patients. The gene encoding this 30-kDa antigen had high sequence similarity with genes encoding putative membrane proteins of bacteria. To evaluate whether the 30-kDa protein can be applied in serological testing for H. cinaedi infections, the recombinant protein was expressed in Escherichia coli as a His-tagged fusion protein and purified by Ni(2+) affinity chromatography. Western blot analysis revealed strong immunoreactivity of the 31-kDa fusion protein with serum antibody from patients infected with H. cinaedi, but such an immunoreaction was absent or was very weak with uninfected control serum. An enzyme-linked immunosorbent assay using this H. cinaedi major antigen showed significantly high antibody titers for H. cinaedi-infected subjects compared with those of various control groups. We therefore conclude that the 30-kDa putative membrane protein is a major antigen of H. cinaedi and is useful for immunological and serological testing for clinical diagnosis and for further epidemiological study of H. cinaedi infection in humans.
嗜柠檬酸弯曲杆菌感染如今被认为是一种日益重要的新发疾病。然而,其发病机制和流行病学特征尚未完全明确。在此,我们研究了嗜柠檬酸弯曲杆菌的抗原蛋白以及嗜柠檬酸弯曲杆菌感染患者对其的免疫反应。我们从一株嗜柠檬酸弯曲杆菌临床分离株构建了嗜柠檬酸弯曲杆菌基因组文库,并表达了多种嗜柠檬酸弯曲杆菌重组蛋白。我们鉴定出一种由嗜柠檬酸弯曲杆菌基因组中一个822 bp编码的30 kDa蛋白为主要抗原,该抗原能被来自经嗜柠檬酸弯曲杆菌免疫的兔子及嗜柠檬酸弯曲杆菌感染患者的血清特异性识别。编码这种30 kDa抗原的基因与编码细菌假定膜蛋白的基因具有高度序列相似性。为评估该30 kDa蛋白是否可应用于嗜柠檬酸弯曲杆菌感染的血清学检测,将该重组蛋白在大肠杆菌中表达为His标签融合蛋白,并通过Ni(2+)亲和层析进行纯化。蛋白质印迹分析显示,31 kDa融合蛋白与嗜柠檬酸弯曲杆菌感染患者的血清抗体具有强烈的免疫反应性,但与未感染的对照血清则无此反应或反应非常微弱。使用这种嗜柠檬酸弯曲杆菌主要抗原进行的酶联免疫吸附测定显示,与各个对照组相比,嗜柠檬酸弯曲杆菌感染受试者的抗体滴度显著更高。因此,我们得出结论,30 kDa假定膜蛋白是嗜柠檬酸弯曲杆菌的主要抗原,可用于免疫和血清学检测,以进行临床诊断及对人类嗜柠檬酸弯曲杆菌感染的进一步流行病学研究。