SRE1 Regulates Iron-Dependent and -Independent Pathways in the Fungal Pathogen Histoplasma capsulatum
SRE1 Regulates Iron-Dependent and -Independent Pathways in the Fungal Pathogen Histoplasma capsulatum
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DOI：
10.1128/ec.05274-11
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Sil, Anita
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作者：
Hwang, Lena H.;Seth, Erica;Sil, Anita
铁获取基因的调节对于在铁限制条件（以获取必需铁）和铁充足条件（以限制铁毒性）下的微生物存活至关重要。在真菌中，铁获得基因在铁充足的条件下被保守的加塔转录调节因子抑制。在这里，我们调查的作用，这种转录因子，SRE 1，在细胞反应的真菌病原体荚膜组织胞浆菌铁。我们发现，SRE 1水平减少RNA干扰的细胞无法抑制铁载体生物合成和利用基因的存在下，丰富的铁，从而产生铁载体，即使在铁充足的条件下。在这些基因的启动子中发现的含有GATA的共有位点的突变也导致在铁充足的条件下不适当的基因表达。微阵列分析比较控制和SRE 1-耗尽菌株的铁限制或丰富的条件下，发现铁响应基因和SRE 1依赖基因，其中包括不同的，但重叠的集。铁响应基因包括那些编码推定的氧化还原酶，代谢和线粒体酶，超氧化物歧化酶，和亚硝化应激反应基因; Sre 1依赖基因的不同功能。受铁水平和Sre 1调控的基因包括所有的铁载体生物合成基因、参与还原铁获得的基因、铁响应转录因子和两种过氧化氢酶。基于转录谱和表型分析，我们得出结论，Sre 1在传统铁响应基因和铁非依赖性途径（例如细胞形态调节）的调节中发挥着关键作用。这些数据突出了Sre 1直系同源物对真菌生物学的影响超出铁调节子的认识。
Regulation of iron acquisition genes is critical for microbial survival under both iron-limiting conditions (to acquire essential iron) and iron-replete conditions (to limit iron toxicity). In fungi, iron acquisition genes are repressed under iron-replete conditions by a conserved GATA transcriptional regulator. Here we investigate the role of this transcription factor, Sre1, in the cellular responses of the fungal pathogen Histoplasma capsulatum to iron. We showed that cells in which SRE1 levels were diminished by RNA interference were unable to repress siderophore biosynthesis and utilization genes in the presence of abundant iron and thus produced siderophores even under iron-replete conditions. Mutation of a GATA-containing consensus site found in the promoters of these genes also resulted in inappropriate gene expression under iron-replete conditions. Microarray analysis comparing control and SRE1-depleted strains under conditions of iron limitation or abundance revealed both ironresponsive genes and Sre1-dependent genes, which comprised distinct but overlapping sets. Iron-responsive genes included those encoding putative oxidoreductases, metabolic and mitochondrial enzymes, superoxide dismutase, and nitrosative-stressresponse genes; Sre1-dependent genes were of diverse functions. Genes regulated by iron levels and Sre1 included all of the siderophore biosynthesis genes, a gene involved in reductive iron acquisition, an iron-responsive transcription factor, and two catalases. Based on transcriptional profiling and phenotypic analyses, we conclude that Sre1 plays a critical role in the regulation of both traditional iron-responsive genes and iron-independent pathways such as regulation of cell morphology. These data highlight the evolving realization that the effect of Sre1 orthologs on fungal biology extends beyond the iron regulon.