Author ORCID Identifier
https://orcid.org/0000-0002-3600-1537
Date of Graduation
5-2020
Document Type
Dissertation (PhD)
Program Affiliation
Microbiology and Molecular Genetics
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Michael C Lorenz, PhD
Committee Member
Ambro van Hoof, PhD
Committee Member
Anne Marie Krachler, PhD
Committee Member
Nicholas De Lay, PhD
Committee Member
Shane Cunha, PhD
Abstract
Candida albicans is a polymorphic unicellular fungus that has evolved to proficiently colonize and infect mammals. A common constituent of the microbiome in the GI tract, mouth, vagina, and skin, C. albicans is also an opportunistic pathogen capable of causing a variety of mucosal infections and the life-threatening disseminated candidiasis. Systemic C. albicans infections are a serious and growing issue; the fungus is the fourth most common cause of nosocomial bloodstream infections which has a mortality rate reaching 50%. As antifungal resistance continues to rise, it is critical that I understand the molecular basis of disseminated fungal infections.
The phagocytes of the immune system are especially important for preventing disseminated infection. Macrophages are employed to clear pathogens in the harsh environment of a phagosome, but C. albicans, as an adaptable opportunist, is capable of surviving macrophage attack to continue dissemination. The Lorenz Lab and other leading labs in the field have identified that C. albicans rapidly adapts to the macrophage phagosome by upregulating alternative carbon utilization processes. The utilization of three alternative carbon sources particularly contribute to C. albicans pathogenesis: carboxylic acids, amino acids, and N-acetylglucosamine. Studied individually, utilization of each carbon source appears to equally contribute to pathogenesis, although mutants defective in any one carbon utilization pathway display only modest attenuation.
Keywords
Fungal pathogenesis, alternative carbon metabolism, Candida albicans, host-microbe interactions, innate immunology, amino acids, N-acetylglucosamine, carboxylic acids