Lawson Jonathan N, Lyons C Rick, Johnston Stephen Albert
Center for Biomedical Inventions, The University of Texas-Southwestern Medical School, Dallas, Texas, USA.
DNA Cell Biol. 2006 Nov;25(11):608-16. doi: 10.1089/dna.2006.25.608.
Yersinia pestis, the causative agent of plague, can be transmitted by infected flea bite or inhaled aerosol. Both routes of infection have a high mortality rate, and pneumonic infections of Y. pestis represent a significant concern as a tool of bioterrorism. Understanding the transcriptional program of this pathogen during pulmonary infection should be valuable in understanding plague pathogenesis, as well as potentially offering insights into new vaccines and therapeutics. Toward this goal we developed a long oligonucleotide microarray to the plague bacillus and evaluated the expression profiles of Y. pestis in vitro and in the mouse pulmonary infection model in vivo. The in vitro analysis compared expression patterns at 27 versus 37 degrees C, as a surrogate of the transition from the flea to the mammalian host. The in vivo analysis used intranasal challenge to the mouse lung. By amplifying the Y. pestis RNA from individual mouse lungs we were able to map the transcriptional profile of plague at postinfection days 1 to 3. Our data present a very different transcriptional profile between in vivo and in vitro expression, suggesting Y. pestis responds to a variety of host signals during infection. Of note was the number of genes found in genomic regions with altered %GC content that are upregulated within the mouse lung environment. These data suggest these regions may provide particularly promising targets for both vaccines and therapeutics.
鼠疫耶尔森菌是鼠疫的病原体，可通过受感染跳蚤叮咬或吸入气溶胶传播。这两种感染途径的死亡率都很高，鼠疫耶尔森菌的肺部感染作为一种生物恐怖主义工具，是一个重大问题。了解这种病原体在肺部感染期间的转录程序，对于理解鼠疫发病机制以及可能为新型疫苗和治疗方法提供见解具有重要价值。为实现这一目标，我们开发了一种针对鼠疫杆菌的长寡核苷酸微阵列，并在体外和小鼠肺部感染体内模型中评估了鼠疫耶尔森菌的表达谱。体外分析比较了27摄氏度与37摄氏度时的表达模式，以此作为从跳蚤到哺乳动物宿主转变的替代指标。体内分析采用鼻内接种小鼠肺部。通过扩增来自单个小鼠肺部的鼠疫耶尔森菌RNA，我们能够绘制出感染后第1至3天鼠疫的转录谱。我们的数据显示，体内和体外表达之间的转录谱差异很大，这表明鼠疫耶尔森菌在感染期间对多种宿主信号有反应。值得注意的是，在小鼠肺部环境中上调的、基因组区域中%GC含量发生改变的基因数量。这些数据表明，这些区域可能为疫苗和治疗方法提供特别有前景的靶点。
