Francisella Genomics

描述(申请人提供)：本项目的目标是确定图拉氏菌亚种Holarctica的DNA序列，该亚种是图拉热症的病原体。图拉氏丝虫已被列为A类精选制剂，对军事和民用生物恐怖主义构成严重威胁。目前正在对图拉氏丝虫的两个菌株进行测序：一个是高毒力的A型菌株，另一个是用作活疫苗的B型(Holarctica)菌株。该项目将确定疫苗株亲本的基因组序列。这种毒株预计将保留疫苗毒株中已改变的完整毒力因子，从而导致其减毒。因此，将该序列与活疫苗毒株以及A型毒株的序列进行比较，将确定毒力因子的候选基因。此外，在未来的研究中，来自接种疫苗的个体的血清应该有助于利用B型毒株的基因组序列来识别抗原。基因组研究的早期结果表明，与其他细菌基因组相比，图拉氏F菌含有较高比例的独特基因。因此，了解图拉氏丝孢杆菌菌株的全基因组序列对于了解其毒力机制是必要的。

DESCRIPTION (provided by applicant): The goal of this project is to determine the DNA sequence of Francisella tularensis subspecies holarctica, the causative agent of tularemia. F. tularensis has been classified as a Category A Select Agent posing a serious military and civilian bioterrorism threat. Two strains of F. tularensis are currently being sequenced: a highly virulent type A strain and a type B (holarctica) strain used as a live vaccine. This project will determine the sequence of the genome of the parent of the vaccine strain. This strain is expected to retain intact virulence factors that have been altered in the vaccine strain, leading to its attenuation. Thus comparison of this sequence with that of the live vaccine strain as well as the type A strain will identify candidate genes for virulence factors. Moreover, sera from vaccinated individuals should be useful in identifying antigens in future studies, using the genomic sequence of the type B strain. Early results from genomic studies suggest that F. tularensis contains a high proportion of unique genes compared to other bacterial genomes. Therefore, knowledge of the complete genome sequences of F. tularensis strains is needed for the understanding of the virulence mechanisms.