Genome Analysis of Streptococcus agalactiae

描述(申请人提供)：B组链球菌(GBS)或 无乳链球菌溶血能力弱，兼性厌氧 革兰氏阳性球菌，在过去的50年里出现了 新生儿败血症、肺炎和脑膜炎的重要细菌原因。GBS 占新生儿细菌感染的30%-50%， 成人GBS感染也已被注意到。这证明了GBS 感染仍然是一个重要的公共卫生问题。 我们建议对Ia型无乳链球菌2.1Mb基因组进行测序 A909使用全基因组随机散弹枪方法。然后我们将使用决赛 汇编的序列及其完整的注释以执行详细的比较 Ia血清型与其他引起肺炎和肺炎的细菌的基因组学分析 脑膜炎。这些分析将允许识别共同的毒力决定因素 由所有生物体或特定于个别生物体。这些决定因素将是 和琼斯博士和鲁本斯有关系吗？签名标签诱变试验 和TnPhoZ翻译融合(分泌蛋白的鉴定)突变体 通过在菌株A909中插入转座子构建文库。区域 将插入的转座子与基因组序列进行比对以识别 基因受到了影响。在不同血清型之间保留的突变体的子集将是 在大鼠脓毒症模型中进行分析，以评估其毒力。 这一合作努力将为未来提供广泛的初步数据 关于理解无乳链球菌致病机理的建议 感染。

DESCRIPTION (provided by applicant): Group B streptococci (GBS) or Streptococcus agalactiae are weakly beta-hemolytic, facultatively anaerobic Gram-positive cocci, which have emerged over the past 50 years as the most significant bacterial cause of neonatal sepsis, pneumonia, and meningitis. GBS account for 30-50 percent of neonatal bacterial infections and increases in adult GBS infections have also been noted. This demonstrates that GBS infections remain an important public health problem. We propose to sequence the 2.1 Mb genome of S. agalactiae serotype Ia strain A909 using a genome-wide random shotgun approach. We will then use the final assembled sequence and its complete annotation to perform detailed comparative genomics analyses between serotype Ia and other organisms causing pneumonia and meningitis. These analyses will allow to identify virulence determinants shared by all organisms or specific to individual ones. These determinants will be related to Drs. Jones and Rubens? experiments on signature tagged mutagenesis and TnphoZ translational fusion (identification of secreted proteins) mutant libraries constructed through transposon insertions in strain A909. Regions where transposons inserted will be aligned to the genome sequence to identify the genes affected. A subset of the mutants conserved across serotypes will be analyzed in the rat sepsis model to evaluate their virulence. This collaborative effort will provide extensive preliminary data for future proposals relevant to understanding the pathogenesis of S. agalactiae infections.