The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae
The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae
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DOI：
10.1128/iai.01821-06
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Schmitt, Michael P.
中科院分区：
文献类型：
--
作者：
Bibb, Lori A.;Kunkle, Carey A.;Schmitt, Michael P.
白喉棒状杆菌hmuO基因的转录，其编码参与血红素铁利用的血红素加氧酶，以血红素或血红蛋白依赖的方式部分地被双组分系统ChrA-ChrS激活。chrA或chrS基因的突变导致C.白喉;然而，观察到在突变体中维持了显著水平的血红蛋白依赖性表达，表明另外的激活剂参与调节。对C.白喉基因组序列揭示了第二个双组分系统，由DIP 2268和DIP 2267编码，分别与ChrS和ChrA具有相似性;我们将这些基因命名为hrrS（DIP 2268）和hrrA（DIP 2267）。hmuO启动子表达的分析表明，血红蛋白依赖性的活动被完全废除的菌株，从这两个chrA-chrS和hrrA-hrrS双组分系统被删除。类似地，传感器激酶基因chrS和hrrS或编码应答调节因子chrA和hrrA的基因的缺失也消除了hmuO启动子处的血红蛋白依赖性激活。我们还表明，调控ChrA-ChrS和HrrA-HrrS参与血红蛋白依赖性抑制的启动子上游的hemA，它编码血红素生物合成酶。的ChrA-ChrS和HrrA-HrrS系统之间的串扰的证据。总之，这些研究结果表明，ChrA-ChrS和HrrA-HrrS调节系统是至关重要的完全血红蛋白依赖性激活的hmuO启动子，也表明，这些双组分系统参与了复杂的机制，调节血红素稳态在C。白喉
Transcription of the Corynebacterium diphtheriae hmuO gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the chrA or the chrS gene resulted in a marked reduction of hemoglobin-dependent activation at the hmuO promoter in C. diphtheriae; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the C. diphtheriae genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes hrrS (DIP2268) and hrrA (DIP2267). Analysis of hmuO promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the chrA-chrS and the hrrA-hrrS two-component systems were deleted. Similarly, deletion of the sensor kinase genes chrS and hrrS or the genes encoding both of the response regulators chrA and hrrA also eliminated hemoglobin-dependent activation at the hmuO promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of hemA, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the hmuO promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in C. diphtheriae.