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EXPLORING MYCOBACTERIOPHAGE-ENCODED CYTOTOXINS

Ko, Ching-Chung (2018) EXPLORING MYCOBACTERIOPHAGE-ENCODED CYTOTOXINS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

More than 1400 mycobacteriophage genomes have been completely sequenced to date. Comparative genomic analyses of the mycobacteriophages have revealed their highly diverse nature. Bioinformatics tools, however, were unable to assign functions to the majority of the mycobacteriophage-encoded genes, and thus the mycobacteriophage genomes provide a rich resource for insights into the biology of the phages and their hosts. This project investigates mycobacteriophage-encoded genes that impair the growth of the mycobacterial hosts. A total of 200 mycobacteriophage-encoded genes were screened for toxicity, identifying 21 toxic genes and 23 inhibitory genes. Based on PSI-BLAST and HHpred predictions, these toxic/inhibitory proteins have very different potential functions. At the same time, half of the toxic/inhibitory proteins have no predicted functions. Using co-immunoprecipitation assays, the interacting targets for two of the toxic proteins, Fruitloop gp52 and Wildcat gp13 were identified as Wag31 and MSMEG_1285, respectively. Identifying the basis of mycobacteriophage-encoded toxic protein action may provide insights into phage-host interaction, and into multiple processes that could be targeted for development of new anti-tuberculosis drugs.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ko, Ching-Chungchk56@pitt.educhk560000-0002-8950-7128
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHatfull, Grahamgfh@pitt.edu
Committee MemberPeebles, Craigcpeebles@pitt.edu
Committee MemberKhan, Saleemkhan@pitt.edu
Committee MemberBerman, Andreaajb190@pitt.edu
Committee MemberVanDemark, Andrewandyv@pitt.edu
Committee MemberHendrix, Roger (in memoriam)
Date: 31 January 2018
Date Type: Publication
Defense Date: 2 November 2017
Approval Date: 31 January 2018
Submission Date: 6 December 2017
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 126
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Mycobacteriophage, Mycobacterium, Tuberculosis, Cytotoxin, Phage
Date Deposited: 31 Jan 2018 17:35
Last Modified: 31 Jan 2018 17:35
URI: http://d-scholarship.pitt.edu/id/eprint/33578

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