Document Type

Honors Thesis

Major

Biochemistry

Advisor(s)

Sally Molloy

Committee Members

Keith Hutchinson, Benjamin King, Melissa Ladenheim, Melody Neely

Graduation Year

May 2021

Publication Date

Spring 5-2021

Abstract

Mycobacterium abscessus (Mab) is an emerging pathogen that can cause pulmonary, skin and disseminating infections. It is one of the most drug-resistant pathogens and infections typically result in high morbidity and mortality. Understanding mechanisms of antibiotic resistance is critical for developing more effective treatments. Prophage, integrated viral genomes, are known to contribute to bacterial virulence and antibiotic resistance, yet Mab prophages remain largely uncharacterized.My research aims to characterize the diversity of the novel cluster MabR prophage genomes. The Molloy lab has demonstrated that the prophage McProf increases mycobacterial resistance to antibiotics. Using the McProf prophage genome sequence, we probed the PATRIC M. abscessus database to identify bacterial strains that carry prophage genomes related to McProf. We identified 25 related genomes, 8 of which were unique. This group of prophages are genetically distinct from prophages already described and we assigned them to a new cluster, MabR. Prophage genome ends were defined, and prophage sequences were extracted from bacterial genomes. MabR genomes are highly conserved, particularly across the structural genes in the right arm and the immunity cassette in the left arm.All nine genomes share a tyrosine-integrase and nearly identical attachment sites.All nine members share one of two types of Type VII secretion system polymorphic toxin systems, adjacent to the right attachment site that potentially improve fitness of the bacterial host. In future research we will investigate the role of MabR polymorphic toxins in drug resistance and bacterial fitness.

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