Cui Shuna, Hassan Rabeay Y A, Heintz-Buschart Anna, Bilitewski Ursula
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Huaihai Road 11, 225001 Yangzhou, China.
Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany.
Molecules. 2016 Jan 28;21(2):162. doi: 10.3390/molecules21020162.
The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-α and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Δcos1 and Δsln1 were also observed. Our results thus indicate a new bio-activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans.
白色念珠菌是人类最常见的机会性真菌病原体，其引起的感染严重程度需要快速有效的抗真菌治疗。一种有效的方法是控制病原体的毒力因子。因此，本研究检测了大豆中天然存在的异黄酮染料木黄酮对白色念珠菌的影响。然后将经染料木黄酮处理的白色念珠菌细胞暴露于巨噬细胞。虽然未观察到对白色念珠菌生长速率的抑制作用，但已观察到巨噬细胞免疫反应增强，表现为吞噬作用以及细胞因子TNF-α和IL-10的释放。杀菌剂咯菌腈或异菌脲可模拟染料木黄酮对增强吞噬作用的影响，它们抑制组氨酸激酶Cos1p并导致HOG途径激活。蛋白质印迹结果显示，白色念珠菌野生型菌株在与染料木黄酮孵育后，Hog1p出现明显磷酸化。此外，还观察到染料木黄酮对组氨酸激酶突变体Δcos1和Δsln1中Hog1p磷酸化的影响。因此，我们的结果表明染料木黄酮通过激活人类病原体白色念珠菌的HOG途径，对白色念珠菌具有一种新的生物活性。
