Portland State University. Department of Biology
Term of Graduation
Date of Publication
Doctor of Philosophy (Ph.D.) in Biology
1 online resource (vi, 174 pages)
Alveolar macrophages attempt to control bacterial infection through a spectrum of defense processes, including induction of apoptosis, autophagy, inflammatory response, and nutrient sequestration. MicroRNAs (miRNAs), a class of small non-coding RNAs, are involved in a spectrum of physiological processes, including immune response to intracellular infections. However, whether microRNAs have any functions in host response to Coxiella burnetii infection is unknown. Coxiella burnetii is a highly infectious intracellular pathogen that causes Q fever, a zoonosis with a worldwide occurrence. In this work, I investigated the functions of miRNAs in host response to C. burnetii infection and found that miRNAs are an integral component of macrophages' stage-specific response to C. burnetii infection, and inhibition of miR-143-3p likely facilitates the pathogen's intracellular growth. I also examined how different isolates of C. burnetii impact host inflammatory responses, and using single-cell analysis discovered that certain subpopulations of infected macrophages are likely more pathogen friendly than others. Additionally, I determined that gallium-protoporphyrin IX (GaPPIX), a heme analog, inhibits C. burnetii's axenic and intracellular growth, and could potentially be used as a therapeutic agent. Together, these results could contribute to the development of novel miRNA- or GaPPIX-based therapeutic agents and could be applied to better understand the virulence strategies of other intracellular pathogens.
© 2021 Madhur Sachan
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Sachan, Madhur, "Exploring miRNA Function and Host Response to Coxiella burnetii Infection" (2021). Dissertations and Theses. Paper 5838.
Available for download on Saturday, August 20, 2022