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泌尿系结石形成的能力而臭名昭著。虽然已经在奇异变形杆菌中鉴定出了几种毒力因子，但最近完成的该基因组测序有可能大大增加我们对奇异变形杆菌发病机制的理解。本研究的第一个具体目的是通过使用微阵列来确定奇异变形杆菌在体外和体内的转录组。这一目标将利用奇异变形杆菌基因组来阐明当该病原体在小鼠泌尿道中生长时，哪些基因表达最高或上调最多。在第二个具体目标中，将构建通过微阵列分析鉴定为体内上调的表面表达蛋白的突变体。将在UTI鼠模型中评估该突变体的体内毒力。最终的特异性目标将测试这种蛋白质的疫苗原性潜力。这些目标的完成可能导致发现奇异变形杆菌疫苗的有用组分。

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.