cAMP regulates vegetative growth and cell cycle in Candida albicans.
We demonstrate here the regulatory role of cAMP in cell cycle of Candida albicans. cAMP was found to be a positive signal for growth and morphogenesis. Phosphodiesterase inhibitor aminophylline exhibited significant effects, i.e., increased growth, as well as induced morphogenesis. Atropine and trifluoperazine negatively regulated (inhibited) growth and did not induce morphogenesis. These changes were attributed to increase in cAMP levels and protein kinase A (PKA) activity in presence of aminophylline, while reduction was observed in atropine and trifluoperazine (TFP) grown cells. Alteration in cAMP signaling pathway affected the cell cycle progression in Candida albicans. Increased cAMP levels in aminophylline grown cells reduced the duration of cell cycle by inciting the cell cycle-specific expression of G1 cyclins (CLN1 and CLN2). However atropine and trifluoperazine delayed the expression of G1 cyclins and hence prolonged the cell cycle. Implication of cAMP signaling pathway in both the cell cycle and morphogenesis further opened the channels to explore the potential of this pathway to serve as a target for development of new antifungal drugs.
Singh
Ajay
A
Department of Biochemistry, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.
Sharma
Sadhna
S
Khuller
Gopal K
GK
D000628:Aminophylline / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology
D014268:Trifluoperazine; D000628:Aminophylline; D001285:Atropine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases