Niche-specific contribution to streptococcal virulence of a MalR-regulated carbohydrate binding protein.
Niche-specific contribution to streptococcal virulence of a MalR-regulated carbohydrate binding protein.
复制标题
MalR 调节的碳水化合物结合蛋白对链球菌毒力的特定贡献。
DOI：
10.1111/j.1365-2958.2011.07708.x
复制
发表时间：
2011
影响因子：
3.6
通讯作者：
Musser,JamesM
中科院分区：
文献类型：
--
作者：
Shelburne3rd,SamuelA;Sahasrobhajane,Pranoti;Suber,Bryce;Keith,DavidB;Davenport,MichaelT;Horstmann,Nicola;Kumaraswami,Muthiah;Olsen,RandallJ;Brennan,RichardG;Musser,JamesM
低G+C革兰氏阳性菌通常含有多个LacI/GalR调节因子家族成员，这些成员通常具有高度相似的氨基末端DNA结合结构域，表明靶DNA序列存在显著重叠。LacI/GalR家族调节因子分解代谢物控制蛋白A（CcpA）是一种全球性的调节因子，在不同的感染部位对GAS毒力有贡献。在此，我们研究了乳糖阻遏蛋白（MalR），另一个LacI/GalR家族成员，在GAS全局基因表达和毒力的作用。MalR失活减少了小鼠口咽部的GAS定植，但对侵袭性感染没有不良影响。MalR转录组仅限于25个基因，并鉴定出高度保守的MalR DNA结合序列。MalR结合序列的变异显著降低了MalR的体外结合。与此相反，CcpA绑定到相同的DNA序列MalR，但容忍的变化，在启动子序列的结合亲和力的变化最小。失活的pulA，一个MalR调控的基因，编码细胞表面碳水化合物结合蛋白，显着减少GAS人上皮细胞粘附和小鼠口咽定植，但不影响GAS侵袭性疾病。这些数据描述了一种分子机制，通过该机制，碳源利用的分级调节以位点特异性方式影响细菌发病机制。
Low G+C Gram‐positive bacteria typically contain multiple LacI/GalR regulator family members, which often have highly similar amino‐terminal DNA binding domains, suggesting significant overlap in target DNA sequences. The LacI/GalR family regulator catabolite control protein A (CcpA) is a global regulator of the Group AStreptococcus(GAS) transcriptome and contributes to GAS virulence in diverse infection sites. Herein, we studied the role of themaltoserepressor (MalR), another LacI/GalR family member, in GAS global gene expression and virulence. MalR inactivation reduced GAS colonization of the mouse oropharynx but did not detrimentally affect invasive infection. The MalR transcriptome was limited to only 25 genes, and a highly conserved MalR DNA‐binding sequence was identified. Variation of the MalR binding sequence significantly reduced MalR bindingin vitro. In contrast, CcpA bound to the same DNA sequences as MalR but tolerated variation in the promoter sequences with minimal change in binding affinity. Inactivation ofpulA, a MalR regulated gene which encodes a cell surface carbohydrate binding protein, significantly reduced GAS human epithelial cell adhesion and mouse oropharyngeal colonization but did not affect GAS invasive disease. These data delineate a molecular mechanism by which hierarchical regulation of carbon source utilization influences bacterial pathogenesis in a site‐specific fashion.