Author ORCID Identifier

https://orcid.org/0000-0003-4082-6029

Date of Award

2026

Document Type

Thesis (Ph.D.)

Department or Program

Microbiology and Immunology

First Advisor

Robert Cramer

Abstract

Saprophytic moulds specialize in decomposing organic matter, cycling carbon and nitrogen in the environment. Aspergillus fumigatus is a saprophytic mould and etiological agent of high-mortality pulmonary mycoses, such as Invasive Pulmonary Aspergillosis (IPA), in immunocompromised patients. Despite being an obligate aerobe, Aspergillus fumigatus can withstand and proliferate in microoxic tensions both in vitro and in vivo infection microenvironments. A. fumigatus strains adapted to low-oxygen environments can display a unique hypoxia-locked colony morphology (H-MORPH) independent of oxygen tension. Moreover, low-oxygen adaptation is a critical virulence factor, however it is not well defined how this adaptation and subsequent physiological rewiring results in increased virulence.

This dissertation explores the complex relationship between low oxygen, carbon metabolism, and nitrogen metabolism that defines a pseudohypoxic physiological state exhibited by low oxygen fit H-MORPH strains of A. fumigatus. This low oxygen rewiring is observed independent of oxygen tension and results in [1] decreased secretion of the extracellular matrix heteropolymer galactosaminogalactan (GAG) and [2] decreased virulence in an immune suppressed murine model of IPA independent of GAG secretion. In leveraging clinical and environmental isolates we begin to investigate the impact of our findings in heterogeneous isolates of A. fumigatus. The results presented in this dissertation contribute to our understanding of low oxygen driven metabolism contributing to A. fumigatus biofilm physiology and consequences for disease.

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