Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicans to iron availability
Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicans to iron availability
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DOI：
10.1186/1471-2180-13-16
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发表时间：
2013-01-24
期刊：
影响因子：
4.2
通讯作者：
Bilitewski, Ursula
中科院分区：
文献类型：
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作者：
Kaba, Hani E. J.;Nimtz, Manfred;Bilitewski, Ursula
背景：铁是几乎所有生物体的必需营养素，为病原体产生铁限制条件是宿主抵抗微生物感染的防御策略之一。过量的铁可能有毒；因此，铁的吸收受到严格控制。机会致病性酵母白色念珠菌的高亲和力铁吸收系统已被证明对于毒力至关重要。已鉴定出铁吸收基因的几种转录因子和调节因子，但对信号通路的了解仍然有限。 Delta hog1 缺失突变体的基因表达谱表明有丝分裂原激活蛋白 (MAP) 激酶 Hog1p 的参与。然而，Hog1p 在白色念珠菌对铁利用率的反应中的功能尚未得到详细研究。因此，我们分析了白色念珠菌对不同铁浓度的表型和分子反应，特别是 Hog1p MAP 激酶模块的活性。结果：当铁离子浓度等于或高于 5 μM 时，我们观察到酵母细胞的絮凝。这种表型取决于 MAP 激酶 Hog1p 和相应的 MAP 激酶激酶 Pbs2p。此外，高细胞外铁离子浓度导致 Hog1p 过度磷酸化。当培养基中的铁离子浓度增加时，我们确定多铜亚铁氧化酶 (MCFO) 蛋白的含量较低，三价铁还原酶活性较低。 Delta hog1 突变体也观察到了这种效应。然而，与野生型细胞相比，Delta hog1 中的 MCFO 蛋白含量和细胞表面铁还原酶活性有所增加。这种效应与生长培养基中铁的可用性无关。结论：在白色念珠菌中，MAP 激酶 Hog1p 是调节生物体对铁可用性反应的网络的一部分。 Hog1p 在高铁浓度下短暂磷酸化，对于絮状表型至关重要。此外，与野生型相比，HOG1 的缺失导致还原性铁摄取系统的成分水平增加，与培养基中的铁浓度无关。然而，低铁浓度对该系统的额外诱导与 HOG1 无关。
Background: Iron is an essential nutrient for almost all organisms, and generating iron limiting conditions for pathogens is one of the host defense strategies against microbial infections. Excess of iron can be toxic; therefore, iron uptake is tightly controlled. The high affinity iron uptake system of the opportunistic pathogenic yeast Candida albicans has been shown to be essential for virulence. Several transcription factors and regulators of iron uptake genes were identified, but the knowledge of signaling pathways is still limited. Gene expression profiling of the Delta hog1 deletion mutant indicated an involvement of the mitogen activated protein (MAP) kinase Hog1p. However, the function of Hog1p in the response of C. albicans to iron availability was not studied in detail. Thus, we analyzed phenotypic and molecular responses of C. albicans to different iron concentrations particularly with respect to the activity of the Hog1p MAP kinase module.Results: We observed flocculation of yeast cells, when the iron ion concentration was equal to or higher than 5 mu M. This phenotype was dependent on the MAP kinase Hog1p and the corresponding MAP kinase kinase Pbs2p. Moreover, high extracellular iron ion concentrations led to hyper-phosphorylation of Hog1p. We determined lower amounts of multicopper ferroxidase (MCFO) proteins and lower ferric reductase activity, when the iron ion concentration in the medium was increased. This effect was also observed for the Delta hog1 mutant. However, the amounts of MCFO proteins and the cell surface ferric reductase activity were increased in the Delta hog1 in comparison to wild type cells. This effect was independent of iron availability in growth media.Conclusions: In C. albicans, the MAP kinase Hog1p is part of the network regulating the response of the organism to iron availability. Hog1p was transiently phosphorylated under high iron concentrations and was essential for a flocculent phenotype. Furthermore, deletion of HOG1 led to increased levels of components of the reductive iron uptake system in comparison to the wild-type, independent of iron concentrations in the media. However, the additional induction of this system by low iron concentrations was independent of HOG1.