Mechanisms by which a fungal HDAC inhibitor suppresses innate immunity in maize

University Of California, San Diego, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): Plant pathogens cause extensive disease resulting in considerable crop loss. This reduction in yield represents a major threat to food security and significantly contributes to malnutrition suffered by more than one billion people. A more complete understanding of the molecular mechanisms regulating plant innate immunity is necessary to inform rational strategies for engineering disease resistant crops. One devastating disease of Zea mays (corn) is caused by the fungal pathogen Cochliobolus carbonum. Intriguingly, the main determinant of C. carbonum virulence is a histone deacetylase inhibitor (HDACi) termed Hc-toxin. How Hc- toxin actually promotes virulence is not known. Additionally, HDACi, including HC-toxin, are being intensively investigated as drugs for the treatment of a range of human diseases including cancer. While HDACi show promise, how they achieve their therapeutic effects remains poorly understood. As regulation of gene expression and other cellular processes are well conserved between plants and animals, insight into HC-toxin function in corn should aid our understanding of HCDAi function in animals. PUBLIC HEALTH RELEVANCE: Plant pathogens cause extensive disease resulting in considerable crop loss, which is a major threat to food security and significantly contributes to malnutrition suffered by more than one billion people. This project is focused on a major corn pathogen, Cochliobolus carbonum that secretes HC-toxin, a potent histone deacetylase inhibitor (HDACi), which like other HDACis is currently being investigated for treatment of cancer and other human diseases. Thus, this study will impact human health by increasing our knowledge of immunity and HDACi function.