Date of Award

8-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair/Advisor

Sourabh Dhingra

Committee Member

Emily Rosowski

Committee Member

Lukasz Kozubowski

Abstract

Aspergillus fumigatus is a saprophytic fungus that can cause a collection of diseases termed aspergillosis; the most severe is invasive pulmonary aspergillosis (IPA). Azole is a major class of antifungal drugs used to treat invasive pulmonary aspergillosis. However, in recent years, there has been an increase in fungal resistance to azole drugs, making the treatment of IPA even more challenging. It is becoming increasingly clear that long non-coding RNAs (lncRNAs), i.e., the RNAs that do not translate into proteins, mediated regulation is vital in stress response and pathogenesis; however, the mechanisms of how lncRNA contribute to fungal stress resistance and pathogenesis remain elusive. Here, I have identified a lncRNA afu-254, which is highly expressed and is differentially regulated in the presence of stresses. Our results show that afu- 254 is indispensable for oxidative stress, azole stress and cell wall stress. Surprisingly, overexpression of afu-254 (OE afu-254), using constitutive gpdA promoter, also made fungus more susceptible to these stresses. Using the Galleria infection model, we show that Δafu-254 and OE afu-254 strains are less virulent than WT. Taken together, this study shows that lncRNA afu-254 plays a role in stress response and in the pathogenesis of A. fumigatus.

Available for download on Sunday, August 31, 2025

Included in

Microbiology Commons

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