Document Type

Honors Thesis

Major

Microbiology

Advisor(s)

Sally Molloy

Committee Members

Edward Bernard, Keith Hutchison, Melody Neely, Sharon Tisher

Graduation Year

May 2020

Publication Date

Spring 5-2020

Abstract

Mycobacterium tuberculosis is the leading cause of death by an infectious disease (MacNeil, 2019). In 2018, 10 million people developed tuberculosis and half a million infections were resistant to antibiotics (WHO, 2019). Nearly all members of the M. tuberculosis complex are lysogens, meaning they carry prophage, or integrated viral genomes within the host genome (Fan et al., 2016). The non-pathogenic vaccine strain (M. bovis Bacillus Calmette–Guérin (BCG)) is the exception, which suggests prophage play a role in virulence (Fan et al., 2016). Because not all prophage encode obvious virulence genes, we hypothesize that prophage impact bacterial virulence by altering bacterial gene expression. By studying gene expression patterns in M. chelonae, a close relative of M. tuberculosis, in the presence and absence of prophage BPs, we determined prophage impact mycobacterial gene expression. Through RNAseq analysis of M. chelonae with or without prophage, we detected significant changes in expression of almost 8% of M. chelonae genes, including the gene whiB7, which is involved in antibiotic resistance. During lysogenic infection of M. chelonae the most highly expressed gene from the BPs prophage was the immunity repressor (gp33). To determine if viral gene products drive changes in expression of whiB7, strains of M. chelonae that express gp33 were created and gene expression and antibiotic resistance analyses were performed. Expression of gp33 did not alter expression of M. chelonae whiB7 nor antibiotic resistance. We are now investigating alternative hypotheses to explain how prophage alter whiB7 expression.

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