Date of Award

5-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Genetics and Biochemistry

Committee Chair/Advisor

Kerry Smith

Committee Member

Kimberly Paul

Committee Member

James Morris

Abstract

Fungal pathogens are a significant threat to public health as they are becoming increasingly common and more resistant to treatment. Cryptococcus neoformans contributes greatly to this threat annually by causing an estimated 278,000 cases of cryptococcal meningitis resulting in approximately 181,000 deaths globally according to the CDC. C. neoformans is ubiquitous across most of the globe and can be found in such places as in trees or soil. Exposure to this fungus is especially dangerous to individuals who are immunocompromised or immunosuppressed. In these cases, inhalation of spores can lead to infection in the lungs. Once in the lungs, C. neoformans is often engulfed by alveolar macrophages intending to destroy the fungus but is often thwarted by pathogenic regulation of the macrophage peroxisome. This allows C. neoformans to travel through the blood brain barrier and infect the brain, leading to deadly cryptococcal meningitis. In shifting from the soil to lung tissue, several metabolic changes occur which allow the fungus to thrive on alternative carbon sources, such as acetate, due to the minimal levels of glucose found in early stages of infection. Acetate needs to be transported across the plasma membrane for activation to acetyl-CoA and utilization in a number of metabolic pathways. Many fungi maintain acetate transporters, many of which belong to the ATO (Ammonia Transport Out) family of transporters. In C. neoformans, the three ATO family members are ATO1 (CNAG_05678), ATO2 (CNAG_05266), and ATO3 (CNAG_04787), which have yet to be characterized. In this study, we examine the phenotypes of single, double, and triple mutants of the C. neoformans ATO genes to begin to elucidate their functions and possible role(s) in virulence.

Author ORCID Identifier

0000-0002-6624-7511

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