Kilmury Sara L N, Twine Susan M
Institute for Biological Sciences, National Research Council Canada Ottawa, ON, Canada.
Front Microbiol. 2011 Jan 7;1:143. doi: 10.3389/fmicb.2010.00143. eCollection 2010.
Francisella tularensis is the causative agent of a spectrum of diseases collectively known as tularemia. The extreme virulence of the pathogen in humans, combined with the low infectious dose and the ease of dissemination by aerosol have led to concerns about its abuse as a bioweapon. Until recently, nothing was known about the virulence mechanisms and even now, there is still a relatively poor understanding of pathogen virulence. Completion of increasing numbers of Francisella genome sequences, combined with comparative genomics and proteomics studies, are contributing to the knowledge in this area. Tularemia may be treated with antibiotics, but there is currently no licensed vaccine. An attenuated strain, the Live Vaccine Strain (LVS) has been used to vaccinate military and at risk laboratory personnel, but safety concerns mean that it is unlikely to be licensed by the FDA for general use. Little is known about the protective immunity induced by vaccination with LVS, in humans or animal models. Immunoproteomics studies with sera from infected humans or vaccinated mouse strains, are being used in gel-based or proteome microarray approaches to give insight into the humoral immune response. In addition, these data have the potential to be exploited in the identification of new diagnostic or protective antigens, the design of next generation live vaccine strains, and the development of subunit vaccines. Herein, we briefly review the current knowledge from Francisella comparative proteomics studies and then focus upon the findings from immunoproteomics approaches.
土拉弗朗西斯菌是一系列统称为兔热病的疾病的病原体。该病原体在人类中的极端毒力,加上低感染剂量和易于通过气溶胶传播,引发了人们对其被用作生物武器的担忧。直到最近,人们对其毒力机制还一无所知,即使到现在,对病原体毒力的了解仍然相对较少。越来越多的土拉弗朗西斯菌基因组序列的完成,结合比较基因组学和蛋白质组学研究,正在为该领域的知识做出贡献。兔热病可用抗生素治疗,但目前尚无获批的疫苗。一种减毒株,即活疫苗株(LVS)已被用于为军队人员和有风险的实验室人员接种疫苗,但出于安全考虑,它不太可能获得美国食品药品监督管理局(FDA)的普遍使用许可。关于用LVS接种疫苗在人类或动物模型中诱导的保护性免疫,人们了解甚少。对受感染人类或接种疫苗小鼠品系血清的免疫蛋白质组学研究,正被用于基于凝胶或蛋白质组微阵列的方法,以深入了解体液免疫反应。此外,这些数据有可能被用于鉴定新的诊断或保护性抗原、设计下一代活疫苗株以及开发亚单位疫苗。在此,我们简要回顾土拉弗朗西斯菌比较蛋白质组学研究的当前知识,然后重点关注免疫蛋白质组学方法的研究结果。