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Toxins 2017, 9(9), 287; doi:10.3390/toxins9090287

The Fungal bZIP Transcription Factor AtfB Controls Virulence-Associated Processes in Aspergillus parasiticus

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA
Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA
Department of Plant Biology, Michigan State University, East Lansing, MI 48824, USA
Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USA
Current address: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14850, USA.
Authors to whom correspondence should be addressed.
Academic Editor: Jiujiang Yu
Received: 30 July 2017 / Revised: 24 August 2017 / Accepted: 7 September 2017 / Published: 16 September 2017
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Fungal basic leucine zipper (bZIP) transcription factors mediate responses to oxidative stress. The ability to regulate stress response pathways in Aspergillus spp. was postulated to be an important virulence-associated cellular process, because it helps establish infection in humans, plants, and animals. Previous studies have demonstrated that the fungal transcription factor AtfB encodes a protein that is associated with resistance to oxidative stress in asexual conidiospores, and AtfB binds to the promoters of several stress response genes. Here, we conducted a gene silencing of AtfB in Aspergillus parasiticus, a well-characterized fungal pathogen of plants, animals, and humans that produces the secondary metabolite and carcinogen aflatoxin, in order to determine the mechanisms by which AtfB contributes to virulence. We show that AtfB silencing results in a decrease in aflatoxin enzyme levels, the down-regulation of aflatoxin accumulation, and impaired conidiospore development in AtfB-silenced strains. This observation is supported by a decrease of AtfB protein levels, and the down-regulation of many genes in the aflatoxin cluster, as well as genes involved in secondary metabolism and conidiospore development. Global expression analysis (RNA Seq) demonstrated that AtfB functionally links oxidative stress response pathways to a broader and novel subset of target genes involved in cellular defense, as well as in actin and cytoskeleton arrangement/transport. Thus, AtfB regulates the genes involved in development, stress response, and secondary metabolism in A. parasiticus. We propose that the bZIP regulatory circuit controlled by AtfB provides a large number of excellent cellular targets to reduce fungal virulence. More importantly, understanding key players that are crucial to initiate the cellular response to oxidative stress will enable better control over its detrimental impacts on humans. View Full-Text
Keywords: aflatoxin; AtfB; virulence-associated processes; oxidative stress; mycotoxin aflatoxin; AtfB; virulence-associated processes; oxidative stress; mycotoxin

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Wee, J.; Hong, S.-Y.; Roze, L.V.; Day, D.M.; Chanda, A.; Linz, J.E. The Fungal bZIP Transcription Factor AtfB Controls Virulence-Associated Processes in Aspergillus parasiticus. Toxins 2017, 9, 287.

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