|Chang, Perng Kuang|
|Luo, Meng -|
Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 6, 2011
Publication Date: January 12, 2011
Citation: Chang, P.-K., Scharfenstein, L.L., Luo, M., Mahoney, N.E., Molyneux, R.J., Yu, J., Brown, R.L., Campbell, B.C. 2010. Loss of msnA, a putative stress regulatory gene, in Aspergillus parasiticus and Aspergillus flavus increased production of conidia, aflatoxins and kojic acid. Toxins. 3:82-104. Interpretive Summary: The molds Aspergillus flavus and A. parasiticus produce carcinogenic aflatoxins that pose a great risk to human and animal health. The synthesis of aflatoxins is considered a defense mechanism against oxidative stress in cells. To better understand the molecular mechanisms that mediate oxidative stress, we disabled a stress related regulator and examined the effect on growth, development, and production of secondary metabolites. Impairment of the regulatory gene severely decreased vegetative growth but elevated sporulation, a process initiated by oxidative stress. The impairment also caused increased production of aflatoxins and kojic acid, a known free radical scavenger. The findings show that oxidative stress is a major determinant of aflatoxin production. This information, used along with other preventive strategies, may help to reduce aflatoxin contamination of host plants in the field.
Technical Abstract: Production of the harmful carcinogenic aflatoxins by Aspergillus parasiticus and Aspergillus flavus has been postulated to be a mechanism to relieve oxidative stress. The msnA gene, the ortholog of Saccharomyces cerevisiae MSN2 associated with multi-stress response, of the two species was disrupted. The msnA mutants ('msnA) exhibited retarded colony growth and increased conidiation. They produced slightly increased amounts of aflatoxins and highly elevated levels of kojic acid, an antioxidant. Microarray assays showed that expression of genes encoding oxidative stress defense enzymes, i.e., superoxide dismutase, catalase A, and cytochrome c peroxidase in A. parasiticus 'msnA and catalase B gene in A. flavus 'msnA was up-regulated. The msnA gene appears to be required for the maintenance of the normal oxidative state. An impairment of msnA resulted in the aforementioned changes, which might be used to combat the increased oxidative stress in the cells.