Pendrak Michael L, Roberts David D
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA.
Med Mycol. 2007 Feb;45(1):61-71. doi: 10.1080/13693780601028691.
Hemoglobin is an abundant protein in the host vascular compartment and a source of iron, heme, and amino acids for many pathogens. The human fungal pathogen Candida albicans uses hemoglobin as an iron source as well as a signaling molecule to alter gene expression and induce adhesion to several extracellular matrix proteins. We now report that hemoglobin can promote true hyphal morphogenesis. Hemoglobin added to yeast cells at 37 degrees C rapidly induced expression of the hypha-specific genes HWP1 and ECE1 coincident with the pattern of hyphal development. A synthetic medium buffered with phosphate at pH 7.2 and containing physiological glucose (5 mM) and low ammonium ion (0.1 mM) was optimal for the response to hemoglobin. High glucose (110 mM), high ammonium ion (20 mM), and 0.1 mM glutamine were all inhibitory. Heme, free globin, or immobilized hemoglobin could not replicate the activity of hemoglobin to induce germ tubes or hypha-specific gene expression at 37 degrees C under optimized conditions. This implicates the previously described Hb-signaling receptor in hyphal formation. This response was also dependent upon the presence of the morphogenesis regulator Efg1p, but the MAP-kinase specific transcription factor Cph1p was not required. These data define a role for the host-factor hemoglobin in Efg1p-dependent hyphal development.
血红蛋白是宿主血管腔室中一种丰富的蛋白质，是许多病原体铁、血红素和氨基酸的来源。人类真菌病原体白色念珠菌将血红蛋白用作铁源以及信号分子，以改变基因表达并诱导其与几种细胞外基质蛋白的黏附。我们现在报告血红蛋白可促进真正的菌丝形态发生。在37摄氏度下添加到酵母细胞中的血红蛋白迅速诱导菌丝特异性基因HWP1和ECE1的表达，这与菌丝发育模式一致。用pH 7.2的磷酸盐缓冲并含有生理葡萄糖（5 mM）和低铵离子（0.1 mM）的合成培养基对血红蛋白反应最为适宜。高葡萄糖（110 mM）、高铵离子（20 mM）和0.1 mM谷氨酰胺均具有抑制作用。在优化条件下，血红素、游离珠蛋白或固定化血红蛋白在37摄氏度下均无法复制血红蛋白诱导芽管或菌丝特异性基因表达的活性。这表明先前描述的血红蛋白信号受体参与菌丝形成。这种反应还依赖于形态发生调节因子Efg1p的存在，但不需要丝裂原活化蛋白激酶特异性转录因子Cph1p。这些数据确定了宿主因子血红蛋白在Efg1p依赖性菌丝发育中的作用。
