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THE ROLE OF pknG IN MYCOBACTERIAL PHYSIOLOGY,
INCLUDING M. tuberculosis
by
Dennis To
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PATHOBIOLOGY)
August 2011
Copyright 2011
Dennis To
Object Description
| Title | The role of pknG in mycobacterial physiology, including M. tuberculosis |
| Author | To, Dennis |
| Author email | dto@usc.edu;dennisto@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-06-03 |
| Date submitted | 2011-07-21 |
| Date approved | 2011-07-22 |
| Restricted until | 2011-07-22 |
| Date published | 2011-07-22 |
| Advisor (committee chair) |
Hofman, Florence Nash, Kevin A. |
| Advisor (committee member) | Finkel, Steven |
| Abstract | Tuberculosis continues to be a major cause of mortality worldwide, killing about two million people every year. The emergence of drug resistant strains of the bacterium has hindered efforts to successfully control the pandemic. The main causative agent, Mycobacterium tuberculosis, employs several strategies that help it survive in host macrophages. Recent studies have shown that the eukaryotic-like serine/threonine protein kinase G (PknG), secreted by M. tuberculosis, can inhibit phagosome-lysosome fusion and mediate intracellular survivability. Through transposon-insertion mutagenesis, a Mycobacterium smegmatis knockout of the pknG gene was generated. This mutant was found to be hypersusceptible to erythromycin, an antimycobacterial agent. This finding suggests that pknG is involved in processes that affect the activity of antimicrobial agents. The objective of the project is to characterize the roles that this gene plays in mycobacterial physiology, which may give us insight to the drug susceptibility and pathogenicity of mycobacteria, including M. tuberculosis. |
| Keyword | serine; threonine; protein kinase; kinase; pknG; mycobacteria; mycobacterium; tuberculosis; smegmatis; antibiotic; antimicrobial; resistance; susceptibility; drug; macrolide; rifampin; rifamycin; biofilm; nitrogen; Krebs; TCA; glyoxylate; NADH; NAD; bacteria; prokaryote; KGD; ketoglutarate; glutamate; glutamine; ammonium; GarA; phosphorylation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | To, Dennis |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-ToDennis-148.pdf |
Description
| Title | Page 1 |
| Full text | THE ROLE OF pknG IN MYCOBACTERIAL PHYSIOLOGY, INCLUDING M. tuberculosis by Dennis To A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PATHOBIOLOGY) August 2011 Copyright 2011 Dennis To |
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