Genomic Approach to Vaccine Design for Proteus mirabilis

描述（由申请人提供）：尿路感染是美国最常见的细菌感染之一，奇异变形杆菌是复杂尿路患者感染的主要原因。这种肠杆菌科的成员因其导致尿路结石形成的能力而臭名昭著。虽然在奇异假单胞菌中已经确定了几个毒力因子，但最近完成的该基因组测序有可能大大增加我们对奇异假单胞菌发病机制的理解。本研究的第一个特定目的是通过使用微阵列来确定P. mirabilis在体外和体内的转录组。这一目标将利用P. mirabilis基因组来阐明当这种病原体在小鼠尿路中生长时，哪些基因表达最多或上调最多。在第二个特异性目标中，将构建一个通过微阵列分析在体内鉴定为上调的表面表达蛋白的突变体。该突变体将在尿路感染小鼠模型中进行体内毒力评估。最后的特异性目标将测试该蛋白的疫苗原性潜力。完成这些目标可能会导致发现一种有用的神奇假单胞菌疫苗成分。

DESCRIPTION (provided by applicant): Urinary tract infections are one of the most common bacterial infections in the U.S. Proteus mirabilis is a major cause of infection in individuals with complicated urinary tracts. This member of the Enterobacteriaceae is notorious for its ability to cause urinary stone formation. Although several virulence factors have been identified in P. mirabilis, the recent completion of the sequencing of this genome has the potential to greatly increase our understanding of P. mirabilis pathogenesis. The first Specific Aim of this study is to determine the transcriptome of P. mirabilis in vitro and in vivo through use of a microarray. This aim will make use of the P. mirabilis genome to elucidate which genes are most highly expressed or most upregulated when this pathogen is grown in the mouse urinary tract. In the second Specific Aim, a mutant of a surface-expressed protein identified as upregulated in vivo by microarray analysis will be constructed. This mutant will be assessed in vivo for virulence in the murine model of UTI. The final Specific Aim will test the vaccinogenic potential of this protein. Completion of these aims may lead to the discovery of a useful component for a P. mirabilis vaccine.