Author ORCID Identifier
https://orcid.org/0009-0002-2187-4367
Date of Award
Summer 8-8-2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biology
First Advisor
Zehava Eichenbaum
Second Advisor
Eric S. Gilbert
Third Advisor
Jorge E. Vidal
Fourth Advisor
Cynthia N. Cornelissen
Abstract
Pathogenic bacteria require iron during growth and have evolved elaborated machinery to obtain iron during infection. Most of the host iron is found in heme bound to hemoglobin. This dissertation uncovers novel mechanisms used by the Gram-positive pathogen, Streptococcus pneumoniae, to leverage the host hemoglobin as an iron source. Chapter 1 describes my contributions to the discovery that hemoglobin provides S. pneumoniae with nutritional iron and serves as a host cue that promotes pneumococcal growth, biofilm development, and adaptation to the host mucosal surfaces. In Chapter 2, I characterize the role of the endogenously produced hydrogen peroxide in iron metabolism, uncovering extracellular heme degradation by S. pneumoniae. In Chapter 3, I investigate the function of Spd_0739 (aka PnrA and Spbhp-37), a ligand-binding protein previously linked to the uptake of nucleosides and heme. I demonstrate that Spd_0739 inhibits iron and heme uptake in S. pneumoniae and that its absence renders the expression of the heme transporter PiuBCDA growth inhibitory. These studies revealed a new connection between iron and nucleotide metabolism in S. pneumoniae and implicate Spd_0739 as a mediator of this association.
DOI
https://doi.org/10.57709/35867609
Recommended Citation
Womack, Edroyal, "Investigation into Metabolism and Signaling of Hemoglobin in Streptococcus pneumoniae." Dissertation, Georgia State University, 2023.
doi: https://doi.org/10.57709/35867609
File Upload Confirmation
1