PERR CONTROLS PEROXIDE- AND IRON- RESPONSIVE EXPRESSION OF OXIDATIVE STRESS DEFENSE GENES IN HELICOBACTER HEPATICUS
PERR CONTROLS PEROXIDE- AND IRON- RESPONSIVE EXPRESSION OF OXIDATIVE STRESS DEFENSE GENES IN HELICOBACTER HEPATICUS
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DOI：
10.1556/eujmi.1.2011.3.5
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发表时间：
2011-09-01
影响因子：
2.2
通讯作者：
Kuipers, E. J.
中科院分区：
文献类型：
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作者：
Belzer, C.;van Schendel, B. A. M.;Kuipers, E. J.
嗜氧小鼠病原体肝螺杆菌的慢性肠道和肝脏定植可导致一系列下消化道炎症性疾病。定植与活跃的细胞免疫反应和氧自由基的产生有关。在定植过程中，肝片吸虫需要应对和响应氧化应激，本文报道了肝片吸虫Perr调节基因(HH0942)在编码过氧化物酶的KATA(HH0043)和ahpC(HH1564)基因表达中的作用。KATA和ahpC的转录受过氧化氢和生长介质中铁限制的诱导。这种对KATA和ahpC的铁和过氧化氢反应的调节是在转录水平上进行的，直接来自基因上游的启动子。Perr基因的失活导致KATA和ahpC转录本及相应蛋白的高水平表达。最后，KATA基因的失活导致肝型肝炎病毒对过氧化氢的敏感性增加，并降低了对空气的耐受性。在肝细胞中，铁代谢和氧化应激防御通过PerR调节蛋白紧密联系在一起。这一调控模式类似于在肠道病原体空肠弯曲菌中观察到的模式，但与在密切相关的人类胃部病原体幽门螺杆菌中观察到的模式形成对比。
Chronic intestinal and hepatic colonization with the microaerophilic murine pathogen Helicobacter hepaticus can lead to a range of inflammatory diseases of the lower digestive tract. Colonization is associated with an active cellular immune response and production of oxygen radicals. During colonization, H. hepaticus needs to cope with and respond to oxidative stress, and here we report on the role of the H. hepaticus PerR-regulator (HH0942) in the expression of the peroxidase-encoding katA (HH0043) and ahpC (HH1564) genes. Transcription of katA and ahpC was induced by hydrogen peroxide, and by iron restriction of growth media. This iron-and hydrogen peroxide-responsive regulation of katA and ahpC was mediated at the transcriptional level, from promoters directly upstream of the genes. Inactivation of the perR gene resulted in constitutive, iron-independent high-level expression of the katA and ahpC transcripts and corresponding proteins. Finally, inactivation of the katA gene resulted in increased sensitivity of H. hepaticus to hydrogen peroxide and reduced aerotolerance. In H. hepaticus, iron metabolism and oxidative stress defense are intimately connected via the PerR regulatory protein. This regulatory pattern resembles that observed in the enteric pathogen Campylobacter jejuni, but contrasts with the pattern observed in the closely related human gastric pathogen Helicobacter pylori.