Montor Wagner R, Huang Jin, Hu Yanhui, Hainsworth Eugenie, Lynch Susan, Kronish Jeannine-Weiner, Ordonez Claudia L, Logvinenko Tanya, Lory Stephen, LaBaer Joshua
Harvard Institute of Proteomics, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Boston Children's Hospital, Boston, MA 02115, USA.
Infect Immun. 2009 Nov;77(11):4877-86. doi: 10.1128/IAI.00698-09. Epub 2009 Sep 8.
Pseudomonas aeruginosa is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis. P. aeruginosa infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported P. aeruginosa PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant (P<0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.
铜绿假单胞菌可导致防御机制受损的个体以及囊性纤维化患者发生潜在的危及生命的感染。铜绿假单胞菌感染的显著特点是对某些已知抗原(如鞭毛蛋白C、弹性蛋白酶、碱性蛋白酶等)出现体液免疫反应。尽管已知多种免疫原性蛋白,但尚未有有效的疫苗获批。在此,我们通过一种名为核酸可编程蛋白阵列的改良蛋白质微阵列方法,对铜绿假单胞菌PAO1的所有262种外膜蛋白和分泌蛋白进行了全面研究。通过这项研究,有可能鉴定出12种能在囊性纤维化患者和急性感染患者中引发适应性免疫反应的蛋白,这为在感染自然病程中哪些细菌蛋白在体内实际被免疫系统识别提供了有价值的信息。这些蛋白在患者和对照中的差异检测结果经统计学分析具有显著意义(P<0.01)。该研究提供了一系列潜在的候选蛋白,可用于改进血清学诊断和开发疫苗。