Standish Alistair J, Stroeher Uwe H, Paton James C
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia.
J Bacteriol. 2007 Aug;189(15):5591-600. doi: 10.1128/JB.00335-07. Epub 2007 May 25.
We have previously shown that CbpA, a major pneumococcal virulence factor, is regulated by the two-component signal transduction system RR/HK06 (A. J. Standish, U. H. Stroeher, and J. C. Paton, Proc. Natl. Acad. Sci. USA 102:7701-7706, 2005). However, additional unidentified regulated factors appeared to be responsible for differences in adherence and the ability of Streptococcus pneumoniae to cause disease in a mouse model. Here, we identified a number of other regulated genes by overexpressing the system. cbpA, along with a cotranscribed upstream gene, showed substantial increases in expression when RR06 was overexpressed in S. pneumoniae strains D39 and TIGR4. However, there were no other similarities between these strains. In D39, rr06 overexpression decreased expression of numerous factors, including the major virulence factor gene pspA. Further investigation of cbpA regulation by RR/HK06, using mutants with mutations in both HK06 and RR06, suggested that rather than the norm, cbpA transcription was activated when RR06 was in the nonphosphorylated form. Although other factors, such as pspA and gls24, are regulated by this system, these genes appear to be repressed when RR06 is in its phosphorylated form.
我们之前已经表明，肺炎球菌主要毒力因子CbpA受双组分信号转导系统RR/HK06调控（A. J. Standish、U. H. Stroeher和J. C. Paton，《美国国家科学院院刊》102:7701 - 7706，2005年）。然而，在小鼠模型中，其他尚未明确的调控因子似乎是肺炎链球菌在黏附及致病能力方面存在差异的原因。在此，我们通过过表达该系统鉴定出了一些其他的调控基因。当RR06在肺炎链球菌菌株D39和TIGR4中过表达时，cbpA以及一个与其共转录的上游基因的表达显著增加。然而，这些菌株之间没有其他相似之处。在D39中，rr06过表达降低了许多因子的表达，包括主要毒力因子基因pspA。使用HK06和RR06均发生突变的突变体对RR/HK06对cbpA的调控进行进一步研究表明，与正常情况相反，当RR06处于非磷酸化形式时，cbpA转录被激活。虽然其他因子，如pspA和gls24受该系统调控，但当RR06处于磷酸化形式时，这些基因似乎被抑制。
