Genistein effects on growth and cell cycle of Candida albicans.
Microbial virulence is generally considered to be multifactorial with infection resulting from the sum of several globally regulated virulence factors. Estrogen may serve as a signal for global virulence induction in Candida albicans. Nonsteroidal estrogens and estrogen receptor antagonists may therefore have interesting effects on yeast and their virulence factors. Growth of C. albicans was monitored by viable plate counts at timed intervals after inoculation into yeast nitrogen broth plus glucose. To determine if increased growth of yeast in the presence of estradiol was due to tyrosine kinase-mediated signaling, we measured growth in the presence of genistein, estradiol or genistein plus estradiol and compared these conditions to controls, which were not supplemented with either compound. Unexpectedly, genistein stimulated growth of C. albicans. In addition, genistein was found to increase the rate of germination (possibly reflecting release from G(0) into G(1) cell cycle phase) and also increased Hsp90 expression, demonstrated by a dot blot technique which employed a commercial primary antibody detected with chemiluminescence with horseradish peroxidase-labeled secondary antibody. These biological effects may be attributable to genistein's activity as a phytoestrogen. In contrast, nafoxidine suppressed growth of Candida and mildly diminished Hsp90 expression. This study raises the possibility of receptor cross-talk between estrogen and isoflavinoid compounds, and antiestrogens which may affect the same signaling system, though separate targets for each compound were not ruled out.
Yazdanyar
A
A
Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, USA.
Essmann
M
M
Larsen
B
B
D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009256:Nafoxidine / Q000494:pharmacology; D009391:Nephelometry and Turbidimetry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
D004965:Estrogen Antagonists; D018841:HSP90 Heat-Shock Proteins; D009256:Nafoxidine; D004958:Estradiol; D019833:Genistein; D011505:Protein-Tyrosine Kinases