Abstract
Trifluoperazine, an anti-calmodulin agent, inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999, without affecting the growth significantly. Culturing the organism for 3 days in the presence of 0.14mm trifluoperazine resulted in a generalized decrease in the production of all aflatoxins; the production of aflatoxin B1, a potent hepatocarcinogen, was inhibited to 88% under such conditions. Culturing 7-day-old preformed cultures in the presence of higher concentrations of trifluoperazine (>1mm) completely abolished production of all aflatoxins including AFB1. The inhibitory influence of trifluoperazine on aflatoxin production was accompanied by calmodulin-dependent phosphorylation of an 85kDa 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.
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References
Adye, J., & Mateles, R.I. 1964 Incorporation of labelled compounds into aflatoxins. Biochimica et Biophysica Acta 86, 418–420.
Bennett, J.W. & Christensen, S.B. 1983 New perspectives on aflatoxin biosynthesis. Advances in Applied Microbiology 29, 53–92.
Beppu, T. 1995 Signal transduction and secondary metabolism: Prospects for controlling productivity. Trends in Biotechnology 13, 264–269.
Billingsley, M.L., Pennypacker, K.R., Hoover, C.G., Brigati, D.J. & Kincaid, R.L. 1985 A rapid and sensitive method for detection and quantification of calcineurin and calmodulin-binding proteins using biotinylated calmodulin. Proceedings of the National Academy of Sciences of the United States of America 82, 7585–7589.
Cheung, W.Y. 1980 Calmodulin plays a pivotal role in cellular regulation. Science 207, 19–27.
Clavero, M., Rocelle, S., Harrison, M.A. and Hung, Y-C. 1994 Aspergillus parasiticus NRRL 2667 growth and aflatoxin synthesis as affected by calcium content and initial spore load in single peanuts. Journal of Food Protection 57, 415–418.
Egan, H. (ed.) 1982 Environmental Carcinogens–Selected methods of analysis; Some mycotoxins, International Agency for Research on Cancer 5, 179–182.
Elisa, F.S., Norman, D.D. & Paul, A.L. 1992 Inhibition of aflatoxin B1 by emetine in stationary cultures of Aspergillus flavus. Mycological Research 96, 385–389.
Ellis, W.O., Smith, J.P. & Simpson, B.K. 1991 Aflatoxins in food: Occurrence, Biosynthesis, Effects on organisms, Detection and methods of control. Critical Reviews in Food Science and Nutrition 30, 403–439.
Gupta, S.R., Prasanna, H.R., Vishwanathan, L. & Venkitasubramanian, T.A. 1975 The effect of inorganic salts and some biologically active important compounds on the incorporation of 1-14C acetate into aflatoxins by the resting mycelia of Aspergillus parasiticus. Zeitschrift für Lebensmittel-Untersuchung und Forschung 157, 19–22.
Hanson, P.I., Kapillof, M.S., Lou, L.L., Rosenfeld, M.G. & Schulman, H. 1989 Expression of multifunctional Ca2+/Calmodulin-dependent protein kinase and mutational analysis of its autoregulation. Neuron 3, 59–70.
Laemmli, U.K. 1970 Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–684.
Maggon, K.K., Gupta, S.K. & Venkitasubramanian, T.A. 1977 Biosynthesis of Aflatoxins. Bacteriological Reviews 41, 822–855.
Muthukumar, G., Nickerson, A.W. & Nickerson, K.W. 1987 calmodulin levels in yeast and filamentous fungi. FEMS Microbiology Letters 41, 253–255.
O'Farrell, P.H. 1975 High resolution two dimensional electrophoresis of proteins. Journal of Biological Chemistry 250, 4007–4021.
Paranjpe, V. & Datta, A. 1990 Role of calmodulin in morphogenesis of candida albicans. In Calcium as an Intracellular Messenger in Eukaryotic Microbes, ed O'Day, D.H. pp. 362–374. Washington DC: American Society for Microbiology.
Schroeder, H.W., Cole, R.J., Grigsby, R.D. & Hein, H.JR. 1974 Inhibition of aflatoxin production and tentative identification of an aflatoxin intermediate ``Versiconal Acetate'' from treatment with Dichlorvos. Applied Microbiology 27, 394–399.
St Leger, R.J., Roberts, D.W. & Staples, R.C. 1989 Calcium and calmodulin-mediated protein synthesis and protein phosphorylation during germination, growth and protease production by Metarhizium anisopliae. Journal of General Microbiology 135, 2141–2154.
Susan, B.R. & Noreen, E.M. 1994 Inhibition of Aflatoxin production by Surfactants. Applied and Environmental Microbiology 60, 106–110.
Zaika, L.L. & Buchanan, R.L. 1987 Review of compounds affecting the biosynthesis or bioregulation of aflatoxins. Journal of Food Protection 50, 691–708.
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Rao, J.P., Sashidhar, R. & Subramanyam, C. Inhibition of aflatoxin production by trifluoperazine in Aspergillus parasiticus NRRL 2999. World Journal of Microbiology and Biotechnology 14, 71–75 (1997). https://doi.org/10.1023/A:1008876517450
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DOI: https://doi.org/10.1023/A:1008876517450