The rtfA gene regulates plant and animal pathogenesis and the synthesis of numerous secondary metabolites in Aspergillus flavus
Committee members: Cary, Jeffrey W.; Limon, Carmen; Yin, Yanbin; Zhou, Shendge.||Advisor: Calvo, Ana M.||Includes bibliographical references.
Abstract
Aspergillus flavus is an opportunistic fungal plant and human pathogen and producer of mycotoxins including aflatoxin B1 (AFB1). As part of our ongoing studies to elucidate biological functions of the A. flavus rtfA gene, we examined its role in pathogenicity of both plant and animal model systems. rtfA encodes a putative RNA-Pol II transcription elongation factor, previously characterized in Saccharomycese cerevisiae, Aspergillus nidulans, Aspergillus fumigatus, where it was shown to regulate several important cellular processes, including morphogenesis, secondary metabolism. In addition, an initial study in A. flavus indicated that rtfA also influences development and production of AFB₁, however its effect on virulence is unknown. The current study revealed that the rtfA gene is indispensable for normal pathogenicity in plants when using peanut seed as infection model, and in animals, as shown in the Galleria mellonella infection model. Interestingly, rtfA positively regulates several processes known to be necessary for successful fungal invasion and colonization of host tissue, such as adhesion to surfaces; protease and lipase activity; cell wall composition and integrity; and resistance to oxidative stress. In addition, metabolomic analysis revealed that A. flavus rtfA affects the production of several secondary metabolites including AFB₁, aflatrem, paxilline, leporins, aflavinines, ditryptophenaline, and aspirochlorine, supporting a role of rtfA as a global regulator of secondary metabolism. Heterologous complementation of an A. flavus deletion rtfA strain with rtfA homologs from A. nidulans or S. cerevisiae did fully rescue wild type phenotype, indicating that these rtfA homologs are functionally conserved between these three species.
