Award Date

May 2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry and Biochemistry

First Committee Member

Ernesto Abel-Santos

Second Committee Member

Ronald Gary

Third Committee Member

Gary Kleiger

Fourth Committee Member

Jeffery Shen

Number of Pages

109

Abstract

Inhalation of Bacillus anthracis spores leads to the most severe form of anthrax. Following phagocytosis by alveolar macrophages, spores germinate inside the phagolysosome. The mechanism used by the newly germinated B. anthracis cells to survive within macrophages is not completely understood.B. anthracis spores contain large concentrations of calcium in complex with dipicolinic acid (Ca-DPA). Upon germination, the cell excretes the large depot of Ca-DPA. DPA is an amphipathic molecule that could act as a buffer and modulate phagolysosome acidification. Intracellular calcium overload can disrupt signaling pathways required for normal macrophage function and trigger cell death. We hypothesized the release of calcium and/or DPA protects newly germinated B. anthracis cells from macrophage action and is a determining factor in anthrax virulence. In this study, we assessed the roles of DPA and cations on B. anthracis spore physiology and cytotoxicity. We generated B. anthracis mutants that produce DPA-less spores. B. anthracis spores with altered cation contents were also generated. We found that both types of spores exhibit profound changes to their dormancy, viability, germination profile, cation content, and heat resistance. However, no changes in cytotoxicity were observed. The results suggest DPA and cations are not contributing factors to B. anthracis virulence and anthrax cytotoxicity but are important to many properties pertaining to spore biology and physiology.

Keywords

Anthrax cytotoxicity; Bacterial spore germination; Spore physiology

Disciplines

Biochemistry | Microbiology | Molecular Biology

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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