Authors
Nelson, Samantha J.Faculty Advisor
Christopher SassettiAcademic Program
Immunology and MicrobiologyUMass Chan Affiliations
Microbiology and Physiological SystemsMorningside Graduate School of Biomedical Sciences
Document Type
Doctoral DissertationPublication Date
2022-10-12
Metadata
Show full item recordAbstract
Tuberculosis, the disease caused by Mycobacterium tuberculosis (Mtb), is the number one cause of death by an infectious agent. Mtb, an obligate pathogen, must compete with the host for nutrients, including for the essential metal, iron. The inability to acquire iron leads to a loss of virulence for Mtb. On the other hand, acquiring excess iron leads to oxidative stress that can damage the bacterium. Therefore, the pathways governing iron homeostasis must be precisely balanced for optimal fitness. Though we know many of the proteins participating in this pathway, we still do not understand several aspects, such as how iron transits the cell envelope or how other stress response pathways affect iron homeostasis. The numerous uncharacterized genes in Mtb, including those required for infection, represent potential participants in this pathway and potential drug targets. In this thesis, we describe two novel players required for iron homeostasis in Mtb. We describe a new role for intramembrane proteolytic signaling and sigma factor regulation in iron homeostasis through the finding that Rip1 and SigL are required for growth in low iron. In addition, we describe a role for the previously uncharacterized protein, Rv3193c, in iron homeostasis. We demonstrate that it is required for infection in mice and a conserved residue of the protein contributes to its function. By characterizing essential pathways such as iron homeostasis, we can better understand the requirements for Mtb growth in the host and develop new treatments to address the global burden of tuberculosis.DOI
10.13028/q93c-yv84Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51492Rights
Copyright © 2022 NelsonDistribution License
https://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.13028/q93c-yv84