All ETDs from UAB

Advisory Committee Chair

Todd J Green

Advisory Committee Members

Champion Deivanayagam

Terje Dokland

Michael J Gray

Chad M Petit

Document Type

Dissertation

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Staphylococcal species such as S. aureus and S. epidermidis are opportunistic pathogens that are the leading causes of nosocomial infections. They have become of growing concern due to the virulence factors that they have acquired as well as their inability to be treated due to resistance to antibiotics. Bacteriophages have increasingly become a popular contender for eliminating these pathogens, however not every phage is suitable for the job. Size of the genome, life cycle, the ability to mobilize genomic material, and host range all factor into how well-suited a phage is to be used as a therapeutic. In this dissertation I describe how I used cryo-electron microscopy, three- dimensional reconstruction, and atomic modeling to determine the structure of multiple phage capsids. I describe the structure of the 12 prolate procapsid and ascertained that though the full head is unique in shape, each capsid monomer still adheres to the conserved HK97 like capsid protein fold. I solved the structure of SaPIbov5 procapsid to high- resolution, which allowed for atomic modeling of the proteins that comprise the procapsid, unveiling a novel mechanism for phage capsid size redirection. Lastly, I report the near- atomic resolution reconstruction of the Andhra phage capsid. This work provides a foundation by which these phages can be assessed for their therapeutic capability.

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