Messick Joanne B, Santos Andrea P
Department of Comparative Pathobiology, Purdue University, 725 Harrison Street, West Lafayette, IN 47907, USA.
Clin Vaccine Immunol. 2011 Aug;18(8):1275-81. doi: 10.1128/CVI.05060-11. Epub 2011 Jun 8.
Mycoplasma haemofelis infection frequently causes anemia in cats. Despite an intense immune response and/or antibiotic treatment, cats often remain asymptomatic carriers following infection. Our hypothesis is that detection of antibodies to M. haemofelis is a sensitive approach for identifying infected cats, particularly carriers. To date, no immunoassay has been developed. This is due largely to the inability to culture M. haemofelis in vitro; hence, a source of antigen is not readily available. The objective of this study was to identify, express, and purify immunogenic proteins of M. haemofelis. To accomplish this, two whole-genomic expression libraries were created in the Lambda ZapII vector and immunoscreened with preimmune plasma, plasma from specific-pathogen-free cats, and pooled acute- and convalescent-phase plasma from experimentally infected cats. The inserts from 21 immunoreactive clones were sequenced, resulting in the identification of 60 genes coding for putative proteins necessary for diverse cellular functions, along with several novel genes of M. haemofelis. Fragments of selected genes based on bioinformatic analyses were PCR amplified, cloned into a high-level protein expression system, and subsequently expressed in Escherichia coli as a His(6)-fusion protein. The recombinant fusion proteins of M. haemofelis were purified and evaluated as an antigen in a Western blot to verify the findings of previous immunoscreening. Together with bioinformatics analyses of individual genes, this approach provided several putative candidate antigens. Five antigens of M. haemofelis were reactive by Western blotting against the immune plasma and negative against nonimmune plasma; these antigens might be useful serologic or even vaccine targets.
溶血支原体感染常导致猫贫血。尽管有强烈的免疫反应和/或抗生素治疗,但猫感染后常成为无症状携带者。我们的假设是,检测针对溶血支原体的抗体是识别受感染猫尤其是携带者的一种敏感方法。迄今为止,尚未开发出免疫测定法。这主要是由于无法在体外培养溶血支原体;因此,抗原来源不易获得。本研究的目的是鉴定、表达和纯化溶血支原体的免疫原性蛋白。为此,构建了两个在Lambda ZapII载体中的全基因组表达文库,并用免疫前血浆、无特定病原体猫的血浆以及实验感染猫的急性期和恢复期混合血浆进行免疫筛选。对21个免疫反应性克隆的插入片段进行测序,鉴定出60个编码多种细胞功能所需假定蛋白的基因,以及溶血支原体的几个新基因。基于生物信息学分析选择的基因片段进行PCR扩增,克隆到一个高水平蛋白表达系统中,随后在大肠杆菌中作为His(6)融合蛋白表达。纯化溶血支原体的重组融合蛋白并在蛋白质印迹中作为抗原进行评估,以验证先前免疫筛选的结果。结合对单个基因的生物信息学分析,该方法提供了几个假定的候选抗原。溶血支原体的五种抗原在蛋白质印迹中与免疫血浆反应,与非免疫血浆无反应;这些抗原可能是有用的血清学甚至疫苗靶点。