Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Heinrichs, David E.

Abstract

Iron is an essential nutrient for the bacterium Staphylococcus aureus. Wild-type S. aureus utilizes various iron acquisition systems to support growth in iron deplete conditions. S. aureus small colony variants (SCVs) are associated with chronic infections, yet the mechanisms by which these variants acquire iron are unknown. Mutation of hemB, involved in heme biosynthesis, generated a stable SCV that was auxotrophic for hemin and formed small colonies on solid media. To support growth under iron deplete conditions, my data revealed that S. aureus hemB synthesizes the siderophore staphyloferrin B, but not staphyloferrin A, although both siderophores could be utilized by the hemB mutant if provided exogenously. Additionally, I demonstrated that the hemB mutant, in comparison to wild-type S. aureus, was defective for xenosiderophore utilization, including the clinically approved drug Desferal. This study yields important insight into the mechanisms by which S. aureus SCVs acquire iron to cause persistent infection.

Summary for Lay Audience

Staphylococcus aureus is a serious threat to human health and can take on a small colony variant (SCV) form. S. aureus SCVs grow slowly and express genes differently than normal S. aureus because of an altered metabolism. SCVs have been linked to chronic S. aureus infections that are difficult to treat. To cause these infections, S. aureus SCVs must get iron from the host because it is an essential nutrient. S. aureus has evolved several ways to acquire iron in the host, such as the use of siderophores which bind iron strongly and carry it into the cell. While the iron acquisition strategies of normal S. aureus have been studied, it is unknown how S. aureus SCVs acquire iron. Here, the iron acquisition strategies of a stable S. aureus SCV, the hemB mutant, were investigated. The S. aureus hemB mutant was found to have a defect in the production of one of the two staphylococcal siderophores, which was related to differences in its metabolism. The hemB mutant used both staphylococcal siderophores, but could not use siderophores from other organisms, unlike like normal S. aureus. Siderophores were not important for the S. aureus hemB mutant in a mouse model of infection and SCVs were less infective than normal S. aureus. This study contributes to our understanding of how S. aureus SCVs acquire iron to cause lasting infections.

Available for download on Wednesday, August 31, 2022

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Bacteriology Commons

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