Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies
Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies
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DOI：
10.1016/s0002-9440(10)62268-7
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发表时间：
2005-02-01
影响因子：
6
通讯作者：
Musser, JM
中科院分区：
文献类型：
--
作者：
Graham, MR;Virtaneva, K;Musser, JM
人们对自然感染过程中细菌对宿主信号反应的分子基础知之甚少。革兰氏阳性细菌病原体 A 组链球菌 (GAS) 会引起人类粘膜、皮肤和危及生命的全身感染。在从咽喉或皮肤感染向侵袭性感染转变的过程中，GAS 必须适应不断变化的环境和宿主因素。为了更好地了解 GAS 如何适应，我们使用转录谱分析和功能分析来研究人类血液中野生型血清型 M1 GAS 菌株的转录组。 GAS 基因表达的整体变化响应人类血液暴露而迅速发生。我们观察到许多可能增强细菌存活的基因的转录增加，包括那些编码超级抗原和由称为 Mga 的多基因激活剂调节的宿主逃避蛋白的基因。 GAS 还协调表达参与寡肽的蛋白水解、运输和分解代谢的基因，以便在这种富含蛋白质的宿主环境中获得氨基酸。将野生型菌株的转录组与在称为 CovR-CovS 的双组分调控系统中突变的同基因缺失突变体 (DeltacovR) 的转录组进行比较，强化了这样的假设：CovR-CovS 在转录组重组过程中在连接关键生物合成、分解代谢和毒力功能方面发挥着重要作用。总而言之，这些数据为致病菌阻碍宿主防御和在人类血液中生存的策略提供了重要的见解。
The molecular basis for bacterial responses to host signals during natural infections is poorly understood. The gram-positive bacterial pathogen group A Streptococcus (GAS) causes human mucosal, skin, and life-threatening systemic infections. During the transition from a throat or skin infection to an invasive infection, GAS must adapt to changing environments and host factors. To better understand how GAS adapts, we used transcript profiling and functional analysis to investigate the transcriptome of a wild-type serotype M1 GAS strain in human blood. Global changes in GAS gene expression occur rapidly in response to human blood exposure. increased transcription was observed for many genes that likely enhance bacterial survival, including those encoding superantigens and host-evasion proteins regulated by a multiple gene activator called Mga. GAS also coordinately expressed genes involved in proteolysis, transport, and catabolism of oligopeptides to obtain amino acids in this protein-rich host environment. Comparison of the transcriptome of the wild-type strain to that of an isogenic deletion mutant (DeltacovR) mutated in the two-component regulatory system designated CovR-CovS reinforced the hypothesis that CovR-CovS has an important role linking key biosynthetic, catabolic, and virulence functions during transcriptome restructuring. Taken together, the data provide crucial insights into strategies used by pathogenic bacte-ria for thwarting host defenses and surviving in human blood.