Genome Analysis of Streptococcus agalactiae

性状（由申请方提供）：B族链球菌（GBS）或 无乳链球菌具有弱β-溶血性，厌氧性 革兰氏阳性球菌，在过去的50年里， 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感染也被注意到。这表明GBS 感染仍然是一个重要的公共卫生问题。 我们建议对2.1Mb的S.无乳血清型Ia株 A909使用全基因组随机鸟枪法。我们将使用最后的 组装序列及其完整注释进行详细比较 血清型Ia和其他引起肺炎的微生物之间的基因组学分析， 脑膜炎这些分析将有助于确定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吗标签诱变实验 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 其中插入的转座子将与基因组序列进行比对， 受影响的基因在血清型之间保守的突变体的子集将被 在大鼠脓毒症模型中分析以评估它们的毒力。 这一合作努力将为今后的研究提供广泛的初步数据。 提出了进一步认识S.无乳 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.