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

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