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首页> 外文期刊>Infection and immunity >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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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

机译：ChrA-ChrS和HrrA-HrrS信号转导系统对于白喉棒状杆菌中hmuO启动子的激活和hemA启动子的抑制是必需的

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摘要

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.
机译：编码参与血红素铁利用的血红素加氧酶的白喉棒杆菌hmuO 基因的转录部分由血红素或血红蛋白依赖性方式被二组分系统ChrA-ChrS激活。 chrA 或 chrS 基因的突变导致 C中 hmuO 启动子的血红蛋白依赖性激活显着降低。白喉;然而，据观察，在突变体中维持了显着水平的血红蛋白依赖性表达，这表明另外的激活剂参与调节。 Bem搜索 C。白喉的基因组序列揭示了由DIP2268和DIP2267编码的第二个双组分系统，分别与ChrS和ChrA相似。我们将这些基因命名为 hrrS （DIP2268）和 hrrA （DIP2267）。对 hmuO 启动子表达的分析表明， chrA - chrS 和 hrrA菌株均完全消除了血红蛋白依赖性活性删除了- hrrS 两部分系统。同样，删除传感器激酶基因 chrS 和 hrrS 或同时编码应答调节因子 chrA 和 hrrA 还消除了 hmuO 启动子上的血红蛋白依赖性激活。我们还表明，调节剂ChrA-ChrS和HrrA-HrrS参与了 hemA 上游启动子的血红蛋白依赖性阻遏，该启动子编码血红素生物合成酶。提供了ChrA-ChrS和HrrA-HrrS系统之间的串扰证据。总之，这些发现表明，ChrA-ChrS和HrrA-HrrS调控系统对于 hmuO 启动子上的血红蛋白依赖性完全活化至关重要，并且还表明这些两组分系统参与了复合物血红素稳态调节的机制白喉。

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