Graduation Year

2025

Date of Submission

12-2024

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Biochemistry

Second Department

Biology

Reader 1

Kyle Jay

Reader 2

Beth Caulkins

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Abstract

Several studies have pioneered the discovery of immunometabolic shifts occurring during microbial infections; however, little work has been done at observing these shifts occurring in polymicrobial infections or occurring in vivo. Here we propose expanding this field by first observing dynamic immunometabolic changes occurring in macrophages when challenged with both Candida albicans and Escherichia coli, first in vitro via RNA-seq and RT-qPCR, and then in vivo while measuring changes in diet and metabolite concentration by utilizing advancements in magnetic resonance spectroscopy and RT-qPCR. We expect to find that when challenged with C. albicans and E. coli, macrophages will undergo Warburg metabolism in an effort to quickly generate energy to fight the infecting microbes. We expect that C. albicans will escape phagocytosis from macrophages and outcompete them for glucose by also upregulating glycolytic genes. While E. coli also prefers glucose as its main source of energy, the competition for glucose will cause E. coli to change its carbon catabolite repression to preferentially utilize more available secondary carbon energy sources, such as utilizing acetate through the glyoxylate cycle. The dual attack of these microbes utilizing different metabolic resources would allow for them to mount a stronger attack on macrophages due to less competition between each other for metabolic resources, causing macrophage death to occur at a faster rate. The discovery of potential synergistic and opposing effect in polymicrobial infections and their dynamic metabolic changes will give us greater insight into the mechanisms utilized by these invading microbes, the immune system’s metabolic response to these threats, and future directions for potential targets of therapeutic intervention.

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