Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (group B streptococcus) in response to incubation with human blood.
Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (group B streptococcus) in response to incubation with human blood.
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DOI：
10.1371/journal.pone.0003143
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发表时间：
2008-09-04
期刊：
影响因子：
3.7
通讯作者：
Musser JM
中科院分区：
文献类型：
--
作者：
Mereghetti L;Sitkiewicz I;Green NM;Musser JM
为了增强对无乳链球菌（B组链球菌，GBS）在侵袭性感染期间如何适应的理解，我们在与人全血孵育后进行了全基因组转录组分析。从在丰富的实验室培养基中生长转变后，GBS转录组在血液接触后迅速发生全球变化。在血液中孵育30分钟后，大多数（83%）显著改变的转录物被下调，并且所有功能类别的基因都被大量表达。我们观察到转录调节因子和应激反应基因表达的复杂动态变化，使GBS迅速适应血液。相对较少的已证实的毒力基因的转录本在前90分钟内上调。然而，一个关键的发现是，编码与宿主凝血/纤溶系统相互作用和细菌-宿主相互作用的蛋白质的基因被迅速上调。参与碳水化合物代谢的基因也发生了广泛的转录变化，包括参与发病机制的多功能蛋白质和调节因子。最后，我们发现，与严重感染和高热患者（40°C）更接近的孵育温度会导致GBS转录组相对于正常体温（37°C）的额外差异。总之，这些数据提供了广泛的新信息，GBS暴露于人类血液中的转录适应，在GBS发病机制的侵袭性疾病的关键步骤，并确定了许多新的线索，分子发病机制的研究。
To enhance understanding of how Streptococcus agalactiae (group B streptococcus, GBS) adapts during invasive infection, we performed a whole-genome transcriptome analysis after incubation with whole human blood. Global changes occurred in the GBS transcriptome rapidly in response to blood contact following shift from growth in a rich laboratory medium. Most (83%) of the significantly altered transcripts were down-regulated after 30 minutes of incubation in blood, and all functional categories of genes were abundantly represented. We observed complex dynamic changes in the expression of transcriptional regulators and stress response genes that allow GBS to rapidly adapt to blood. The transcripts of relatively few proven virulence genes were up-regulated during the first 90 minutes. However, a key discovery was that genes encoding proteins involved in interaction with the host coagulation/fibrinolysis system and bacterial-host interactions were rapidly up-regulated. Extensive transcript changes also occurred for genes involved in carbohydrate metabolism, including multi-functional proteins and regulators putatively involved in pathogenesis. Finally, we discovered that an incubation temperature closer to that occurring in patients with severe infection and high fever (40°C) induced additional differences in the GBS transcriptome relative to normal body temperature (37°C). Taken together, the data provide extensive new information about transcriptional adaptation of GBS exposed to human blood, a crucial step during GBS pathogenesis in invasive diseases, and identify many new leads for molecular pathogenesis research.
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