title: Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein.
abstract: 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.
authors.affiliation: 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. sncui@yzu.edu.cn.|Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany. sncui@yzu.edu.cn.
authors.forename: Shuna
authors.initials: S
authors.lastname: Cui
authors.affiliation: Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany. rapy78@yahoo.com.|Microanalysis Lab, Applied Organic Chemistry Department, National Research Centre (NRC), El Bohouthst., Dokki, 12622 Giza, Egypt. rapy78@yahoo.com.
authors.forename: Rabeay Y A
authors.initials: RY
authors.lastname: Hassan
authors.affiliation: Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany. anna.buschart@uni.lu.|Eco-Systems Biology Research Group, Luxembourg Centre for Systems Biomedicine, Campus Belval, 7 Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg. anna.buschart@uni.lu.
authors.forename: Anna
authors.initials: A
authors.lastname: Heintz-Buschart
authors.affiliation: Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany. ursula.bilitewski@helmholtz-hzi.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Bilitewski
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002460:Cell Line; D004149:Dioxoles / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004149:Dioxoles; D005656:Fungal Proteins; D006827:Hydantoins; C508609:IL10 protein, human; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000620:Aminoimidazole Carboxamide; D019833:Genistein; C108339:fludioxonil; C033148:iprodione
keywords: Candida albicans; HOG pathway; genistein; pathogen-macrophage interaction
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