RNA-mediated thermoregulation of iron-acquisition genes in Shigella dysenteriae and pathogenic Escherichia coli.

RNA-mediated thermoregulation of iron-acquisition genes in Shigella dysenteriae and pathogenic Escherichia coli.
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DOI:
10.1371/journal.pone.0063781
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Murphy ER
Murphy ER
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kouse AB;Righetti F;Kortmann J;Narberhaus F;Murphy ER

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大多数细菌感染的发生、发展和传播取决于入侵病原体从自然感染过程中遇到的各种环境中获得铁的能力。总的来说,人体内95%的铁在血红素中络合,使血红素成为入侵细菌的宿主相关营养铁的潜在丰富来源。由于血红素仅在宿主体内遇到,病原菌通常调节血红素利用因子的合成,使得在与宿主相关的环境条件下生产最大。本研究探讨了ShuA的调节生产,ShuA是一种外膜受体,需要利用血红素作为营养铁的来源,由志贺氏菌,一种致病性细菌,导致严重的人类腹泻疾病。具体而言,研究了在宿主内感染(37°C)和宿主间传播(25°C)期间遇到的不同环境温度对shuA表达的影响。我们表明,shuA表达受到温度依赖性转录后调节,导致在37°C下ShuA产量增加。观察到的体温调节是由5′非翻译区内的核酸序列介导的。此外,我们还鉴定了肠致病性大肠杆菌orthobacteriumchuA转录本5′端非翻译区的相似核苷酸序列。大肠杆菌,并已证明它也赋予温度依赖性转录后调节的功能。在功能和预测的结构中,shuA和chuA 5′非翻译区内的调控元件非常类似于FourU RNA温度计,这是一种拉链状RNA结构,在低温下封闭Shine-Dalgarno序列。响应于宿主体温的ShuA和ChuA的增加的产生允许在S.病原性E.大肠杆菌菌株会遇到血红素,一种宿主特异性的铁源。
The initiation, progression and transmission of most bacterial infections is dependent upon the ability of the invading pathogen to acquire iron from each of the varied environments encountered during the course of a natural infection. In total, 95% of iron within the human body is complexed within heme, making heme a potentially rich source of host-associated nutrient iron for invading bacteria. As heme is encountered only within the host, pathogenic bacteria often regulate synthesis of heme utilization factors such that production is maximal under host-associated environmental conditions. This study examines the regulated production of ShuA, an outer-membrane receptor required for the utilization of heme as a source of nutrient iron by Shigella dysenteriae, a pathogenic bacterium that causes severe diarrheal diseases in humans. Specifically, the impact of the distinct environmental temperatures encountered during infection within a host (37°C) and transmission between hosts (25°C) on shuA expression is investigated. We show that shuA expression is subject to temperature-dependent post-transcriptional regulation resulting in increased ShuA production at 37°C. The observed thermoregulation is mediated by nucleic acid sequences within the 5′ untranslated region. In addition, we have identified similar nucleotide sequences within the 5′ untranslated region of the orthologous chuA transcript of enteropathogenic E. coli and have demonstrated that it also functions to confer temperature-dependent post-transcriptional regulation. In both function and predicted structure, the regulatory element within the shuA and chuA 5′ untranslated regions closely resembles a FourU RNA thermometer, a zipper-like RNA structure that occludes the Shine-Dalgarno sequence at low temperatures. Increased production of ShuA and ChuA in response to the host body temperature allows for maximal production of these heme acquisition factors within the environment where S. dysenteriae and pathogenic E. coli strains would encounter heme, a host-specific iron source.
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