Date of Award

Spring 5-1-2026

Document Type

Honors Project

Degree Name

Bachelor of Science

Department

Biological Sciences

Department Chair or Program Director

Dianne Baker

First Advisor

Dr. Swati Agrawal

Second Advisor

Dr. Lynn Lewis

Third Advisor

Dr. Kelli Slunt

Major or Concentration

Biology

Abstract

Bacteriophages, or phages, are being piloted as a supplemental or alternative therapeutic to antibiotics against drug-resistant Mycobacterium pathogens, such as M. tuberculosis, which pose a global public health crisis.  Characterizing bacteriophage genomes can provide insights into efficacy in phage therapy before implementation or elucidate new targets to manipulate bacterial growth.  Overexpression of individual phage genes is useful to study a gene product’s function independent of others.  Here, the results of phage Mercurio plasmid library overexpression in plate-based assays are described.  Mercurio infects nonpathogenic Mycobacterium smegmatis and is genetically related to bacteriophages infecting pathogenic Mycobacterium species.  Eleven gene products of 31 total studied inhibited host growth when overexpressed in cytotoxicity assays, and no gene products prevented superinfection by genetically dissimilar phages in defense assays.  Analysis of gene products’ sequences and structures revealed homology to other characterized phage proteins and elucidated new structure-function relationships of previously uncharacterized products.  Potential structural and sequence divergence between phages, unique structural motifs, and broad genomic alterations were identified by synthesizing information provided from these assays and analyses.  Exploring the molecular mechanisms of these gene products will undoubtedly reveal more interactions between phages and their hosts for the advancement of antimycobacterial therapeutics.

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