Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans.
Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans.
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DOI：
10.1371/journal.pbio.0040410
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发表时间：
2006-11
期刊：
影响因子：
9.8
通讯作者：
Kronstad JW
中科院分区：
文献类型：
--
作者：
Jung WH;Sham A;White R;Kronstad JW
铁超载可加重多种感染性疾病，反之，抑制铁是哺乳动物宿主的重要防御策略。铁是新生隐球菌的关键线索，因为真菌感知铁来调节多糖膜的形成，而多糖膜是感染过程中的主要毒力因素。过量的铁加剧了实验性的隐球菌病，这种疾病在撒哈拉以南非洲的流行与艾滋病毒/艾滋病流行背景下铁负荷的营养和遗传方面有关。我们证明了铁反应转录因子Cir1在铬中。新生杆菌控制铁获取基因的调控，从而使突变株对外部铁水平的变化“视而不见”。Cir1还控制已知的病原体的主要毒力因素，包括被膜、细胞壁中抗氧化黑色素的形成，以及在宿主体温下生长的能力。因此，真菌被显著地调整为感知铁作为疾病过程的一部分，正如Cir1突变体的无毒所证实的那样；病原体的这一特征可能为抗真菌治疗提供机会。作者发现了一种铁反应转录因子incr。控制表达的新生杆菌是已知的主要毒力因子。
Iron overload is known to exacerbate many infectious diseases, and conversely, iron withholding is an important defense strategy for mammalian hosts. Iron is a critical cue for Cryptococcus neoformans because the fungus senses iron to regulate elaboration of the polysaccharide capsule that is the major virulence factor during infection. Excess iron exacerbates experimental cryptococcosis and the prevalence of this disease in Sub-Saharan Africa has been associated with nutritional and genetic aspects of iron loading in the background of the HIV/AIDS epidemic. We demonstrate that the iron-responsive transcription factor Cir1 in Cr. neoformans controls the regulon of genes for iron acquisition such that cir1 mutants are “blind” to changes in external iron levels. Cir1 also controls the known major virulence factors of the pathogen including the capsule, the formation of the anti-oxidant melanin in the cell wall, and the ability to grow at host body temperature. Thus, the fungus is remarkably tuned to perceive iron as part of the disease process, as confirmed by the avirulence of the cir1 mutant; this characteristic of the pathogen may provide opportunities for antifungal treatment. The authors identify an iron-responsive transcription factor inCr. neoformans that controls the expression known major virulence factors.
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