First Advisor

Kenneth Stedman

Term of Graduation

Fall 2021

Date of Publication

8-20-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.) in Biology

Department

Biology

Language

English

DOI

10.15760/etd.7709

Physical Description

1 online resource (vi, 174 pages)

Abstract

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.

Rights

© 2021 Madhur Sachan

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Persistent Identifier

https://archives.pdx.edu/ds/psu/36853

Appendix.zip (1710 kB)

Available for download on Saturday, August 20, 2022

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