A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus.
A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus.
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DOI：
10.1038/srep32442
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Shelburne SA
中科院分区：
文献类型：
--
作者：
DebRoy S;Saldaña M;Travisany D;Montano A;Galloway-Peña J;Horstmann N;Yao H;González M;Maass A;Latorre M;Shelburne SA
分解代谢物控制蛋白A（CcpA）是革兰氏阳性菌中高度保守的碳源利用的主要调节因子，但CcpA调节子仍不明确。在本研究中，我们的目的是通过确定CcpA失活对人类主要病原体A组链球菌（GAS）的三种不同血清型的毒力和转录组的影响来阐明CcpA调节子。CcpA失活显着降低气体的毒力在一系列广泛的动物挑战模型一致的想法，CcpA是革兰氏阳性细菌的发病机制是至关重要的。通过比较转录组学，我们确定了GAS CcpA核心调节子富含高度保守的CcpA结合基序（即cre位点）。相反，菌株特异性差异CcpA转录组似乎主要包括受影响的二级网络。通过对核心调节子的分析来完善cre位点组成，促进了修改后的cre共识的发展，该共识有望改善对其他医学相关革兰氏阳性病原体中CcpA靶点的预测。
Catabolite control protein A (CcpA) is a highly conserved, master regulator of carbon source utilization in gram-positive bacteria, but the CcpA regulon remains ill-defined. In this study we aimed to clarify the CcpA regulon by determining the impact of CcpA-inactivation on the virulence and transcriptome of three distinct serotypes of the major human pathogen Group A Streptococcus (GAS). CcpA-inactivation significantly decreased GAS virulence in a broad array of animal challenge models consistent with the idea that CcpA is critical to gram-positive bacterial pathogenesis. Via comparative transcriptomics, we established that the GAS CcpA core regulon is enriched for highly conserved CcpA binding motifs (i.e. cre sites). Conversely, strain-specific differences in the CcpA transcriptome seems to consist primarily of affected secondary networks. Refinement of cre site composition via analysis of the core regulon facilitated development of a modified cre consensus that shows promise for improved prediction of CcpA targets in other medically relevant gram-positive pathogens.
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影响因子：
4.4
作者：
Marciniak BC;Pabijaniak M;de Jong A;Dűhring R;Seidel G;Hillen W;Kuipers OP
通讯作者：
Kuipers OP
影响因子：
3.7
作者：
Brittan, J. L.;Buckeridge, T. J.;Jenkinson, H. F.
通讯作者：
Jenkinson, H. F.
影响因子：
6.7
作者：
Horstmann, Nicola;Saldana, Miguel;Shelburne, Samuel A., III
通讯作者：
Shelburne, Samuel A., III
影响因子：
3.6
作者：
Jones, AL;Knoll, KM;Rubens, CE
通讯作者：
Rubens, CE
影响因子：
3
作者：
Eden, Eran;Navon, Roy;Yakhini, Zohar
通讯作者：
Yakhini, Zohar