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trans-Translation in Mycobacteria: Expression, Regulation,
and The Effects of Ribosome Inhibitors
by
Nadya Andini
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)
December 2012
Copyright 2012
Nadya Andini
Object Description
| Title | trans-translation in mycobacteria: expression, regulation, and the effects of ribosome inhibitors |
| Author | Andini, Nadya |
| Author email | andini@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-08-16 |
| Date submitted | 2012-09-18 |
| Date approved | 2012-09-18 |
| Restricted until | 2012-09-18 |
| Date published | 2012-09-18 |
| Advisor (committee chair) | Hofman, Florence |
| Advisor (committee member) |
Nash, Kevin A. Goodman, Steven |
| Abstract | Unique bacterial process, trans-translation, has been studied to be an important process in many bacteria. However, there was nothing known about the significance of this process in mycobacteria, especially in relation to drug susceptibility. Consistent with findings in Escherichia coli, Salmonella typhimurium, and Synechocystis sp., we found that interfering with the expression of tmRNA and the smpB gene (critical components of trans-translation) in Mycobacterium smegmatis caused increased bactericidal activity of antimicrobial agents that target the ribosomes. Moreover, exposure to ribosome inhibitors increased the expression of tmRNA. This increase was driven by the tmRNA gene promoter which activity seemed to utilize a de-repression mechanism. Not only is trans-translation important to the bacterial response to ribosome inhibitors, evidence from this laboratory suggests that trans-translation is essential in mycobacteria. Thus, we believe that trans-translation may represent a new important target for drug development as interfering with this process would be inhibitory to the cells and would enhance the activity of other clinical important therapeutic agents. |
| Keyword | trans-translation; mycobacteria; tmRNA; macrolides. |
| 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 | Andini, Nadya |
| 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_Volume4/etd-AndiniNady-1206.pdf |
Description
| Title | Page 1 |
| Full text | trans-Translation in Mycobacteria: Expression, Regulation, and The Effects of Ribosome Inhibitors by Nadya Andini 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) December 2012 Copyright 2012 Nadya Andini |
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