Inhibition of aflatoxin production by trifluoperazine in Aspergillus parasiticus NRRL 2999

Trifluoperazine, an anti-calmodulin agent, inhibited aflatoxin production by Aspergillus NRRL 2999, parasiticus without affecting the growth significantly. Culturing the organism for 3 days in the presence of 0.14 mM trifluoperazine resulted in a generalized decrease in the production of all aflatoxins; the production of aflatoxin B-1, a potent hepatocarcinogen, was inhibited to 88% under such conditions. Culturing 7-day-old preformed cultures in the presence of higher concentrations of trifluoperzine (> 1 mM M) completely abolished production of all aflatoxins including AFB(1). The inhibitory influence of trifluoperazine on aflatoxin production was accompanied by calmodulin-dependent phosphorylation of an 85 kDa cytoplasmic calmodulin-binding protein. While the functions of calmodulin in mediating primary events of germination, growth and differentiation in fungi have earlier been reported, the present results indicate a possible role for calmodulin in the production of fungal toxins.