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The role of prophages in Mycobacterium abscessus phage susceptibility

Mahalingam, Vaishnavi (2022) The role of prophages in Mycobacterium abscessus phage susceptibility. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Mycobacterium abscessus infections are common to patients with cystic fibrosis (CF) or non-CF bronchiectasis. These are challenging to manage clinically, being resistant to most antibiotics and refractory to treatment. The therapeutic use of bacteriophages offers a potential clinical alternative. Upon screening over 200 M. abscessus strains for phage infection, great variation in phage susceptibility has been observed, which is a major impediment to broad therapeutic phage use. Sequencing of 82 strains showed that 85% carry integrated prophages, with as many as six in a genome. It is hypothesized that these prophages influence the phage infection profiles, as temperate mycobacteriophages are known to express viral defense mechanisms. Nine lytically growing prophage-derivatives were recovered by spontaneous induction of the M. abscessus isolates, and new lysogenic strains were constructed to test this hypothesis. Twenty-five new M. abscessus lysogens were created using five of these phages and eleven different bacterial strains. Most of these lysogens did not show differences in phage plating efficiencies, but several lysogens carrying a prophage of phiGD24-3 showed increased phage infection, implicating it as a determinant of phage susceptibility. This, interestingly, is inconsistent with the expression of viral defense systems typically observed in lysogens. Phage phiGD24-3 integrates into, and disrupts, an AraC family transcriptional regulator (equivalent of M. abscessus strain ATCC 19977 gene MAB_2445), which could also influence phage susceptibilities. Transcriptome profiling will be used to determine what prophage genes are expressed lysogenically, and how bacterial gene expression is influenced by loss of MAB_2445. These findings will inform future efforts to use these phages therapeutically.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mahalingam, Vaishnavivam57@pitt.eduvam57
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberArndt, Karenarndt@pitt.eduarndt
Committee MemberVan Tyne, DariaVANTYNE@pitt.eduVANTYNE
Committee MemberMolloy, Sallysally.dixon@maine.edu
Thesis AdvisorHatfull, Graham F.gfh@pitt.edugfh
Date: 26 April 2022
Date Type: Publication
Defense Date: 1 April 2022
Approval Date: 26 April 2022
Submission Date: 18 April 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 51
Institution: University of Pittsburgh
Schools and Programs: University Honors College
Degree: BPhil - Bachelor of Philosophy
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: bacteriophages, mycobacteria, Mycobacterium abscessus, phage therapy, prophages
Date Deposited: 26 Apr 2022 13:37
Last Modified: 26 Apr 2022 13:37
URI: http://d-scholarship.pitt.edu/id/eprint/42644

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