Publication Date

2019

Document Type

Dissertation/Thesis

First Advisor

Calvo, Ana M.

Degree Name

Ph.D. (Doctor of Philosophy)

Legacy Department

Department of Biological Sciences

Abstract

In this study, I investigated the role of two different regulatory genes in two different species of pathogenic fungi from the genus Aspergillus. The first study involves a transcriptome analysis of the epigenetic regulator rmtA in the plant pathogen Aspergillus flavus. A. flavus colonizes numerous oil seed crops such as corn, peanuts, treenuts and cotton worldwide, contaminating them with aflatoxins and other harmful potent toxins. Previously our lab characterized the gene rmtA, which encodes an arginine methyltransferase in A. flavus, and demonstrated its role as regulator of the expression of the aflatoxin gene cluster and concomitant synthesis of toxin. Furthermore, our studies revealed that rmtA also controls conidial and sclerotial development. Due to this role as an epigenetic regulator in A. flavus we performed a transcriptome analysis to further ascertain the role rmtA may have on A. flavus. In this analysis we identified over 2000 genes that were rmtA-dependent. Of those genes, we identified those that were involved in production of secondary metabolites, response to environmental stress, and genes active during plant virulence.

The second project that was undergone involves the characterization of the homeobox transcriptional regulator HbxA in the opportunistic human pathogen Aspergillus fumigatus. A. fumigatus is the leading cause of Invasive Aspergillosis which in immunocompromised patients has a mortality rate as high as 90%. Earlier studies showed that HbxA is a global regulator in A. flavus regulating morphological development and secondary metabolism. Here we determined its

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role in A. fumigatus examining whether hbxA influences regulation of asexual development, secondary metabolism, and virulence of this fungus. Our analysis demonstrated removal of hbxA caused a near complete loss of conidial production in the mutant strain as well as a slight defect in colony growth. Other aspects of asexual development are affected as well such as size and germination of the conidial spores. Furthermore, we showed that in A. fumigatus loss of hbxA decreased the expression of the brlA central regulatory pathway involved in asexual development, as well as the expression of the “fluffy” genes flbB, flbD, and fluG. HbxA was also found to be a regulator of secondary metabolism affecting production of multiple secondary metabolites. Using a neutropenic mouse model for infection, the role of hbxA in pathogenicity of A. fumigatus was assayed where hbxA was found to have a negative impact on the virulence of this pathogen.

Extent

107 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

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