Differential regulation of iron- and manganese-specific MtsABC and heme-specific HtsABC transporters by the metalloregulator MtsR of group A Streptococcus
Differential regulation of iron- and manganese-specific MtsABC and heme-specific HtsABC transporters by the metalloregulator MtsR of group A Streptococcus
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DOI：
10.1128/iai.00176-06
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发表时间：
2006-09-01
影响因子：
3.1
通讯作者：
Lei, Benfang
中科院分区：
文献类型：
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作者：
Hanks, Tracey S.;Liu, Mengyao;Lei, Benfang
人类致病菌A组链球菌(GAS)的基因组编码转运蛋白MtsABC、FtsABCD和HtsABC，分别摄取铁和锰离子、铁铬铁和血红素。GAS基因组还编码两个金属调节因子PerR和MtsR。为了了解这些转运蛋白的表达规律，我们构建了一株GAS血清型M1株的mtsR和perR缺失突变体，并检测了缺失突变和Fe3+、Mn2+、Zn2+对mts4、hTSA和FTSB表达的影响。Mn2+显著抑制mtsA转录和mtsA蛋白水平，但不下调hTSA和FTSB的表达。Fe3+可降低mtsA和hTSA的表达，但不影响FTSB的表达。锌离子对上述三个基因的表达均无影响。MtsR的缺失取消了Mn2+和Fe3+对mtsA表达的抑制和Fe3+对hTSA表达的抑制。在皮下感染的小鼠模型中，mtsR的缺失不会显著改变GAS的毒力。PerR基因的缺失不会影响基因对金属离子的反应。在Mn2+或Fe2+存在的情况下，MtsR与MTS启动子区域结合。结果表明，mtsR对mtsABC和htsABC的表达具有差异性调控作用。
The genome of the human pathogen group A Streptococcus (GAS) encodes the transporters MtsABC, FtsABCD, and HtsABC to take up ferric and manganese ions, ferric ferrichrome, and heme, respectively. The GAS genome also encodes two metalloregulators PerR and MtsR. To understand the regulation of the expression of these transporters, the mtsR and perR deletion mutants of a GAS serotype M1 strain were generated, and the effects of the deletions and Fe3+, Mn2+, and Zn2+ on the expression of mts4, htsA, and ftsB were examined. Mn2+ dramatically depresses mtsA transcription and levels of the MtsA protein but does not downregulate the expression of htsA and ftsB. Fe3+ decreases the expression of mtsA and htsA but has no effect on ftsB expression. Zn2+ has no effect on the expression of all three genes. The deletion of mtsR abolishes the Mn2+- and Fe3+-induced depression of mtsA expression and the Fe3+-dependent decrease in htsA expression. The deletion of mtsR does not significantly alter GAS virulence in a mouse model of subcutaneous infection. The deletion of perR does not affect the expression of the genes in response to the metal ions. MtsR binds to the mts promoter region in the presence of Mn2+ or Fe2+. The results indicate that MtsR differentially regulates the expression of mtsABC and htsABC.