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Structural and functional characterization of the ESX-3 secretion system in mycobacteria Tan, Yigeng
Abstract
Mycobacteria, including the pathogenic species Mycobacterium tuberculosis (Mtb), possess a unique cell envelope structure that confers resistance to environmental stresses and antimicrobial agents. Mtb, the causative agent of tuberculosis (TB), is a global health concern with increasing drug resistance. The ESX-3 secretion system found in Mtb and other mycobacteria plays a crucial role in the secretion of effector proteins that confer pathogenicity. This thesis focuses on studying the ESX-3 secretion system in mycobacteria by: 1) determining the localization of the secreted substrates PE5-PPE4 in M. smegmatis, and 2) characterizing the in vivo structure of the ESX-3 from Mtb. Briefly, the ESX-3 substrate PPE4 was found localized to the MOM of M. smegmatis, and ESX-3 from Mtb was found to localize to the poles of M. marinum forming a putative trans envelope structure. Together, this research contributes to our understanding of the role of ESX-3 in pathogenicity of mycobacteria and may inform the development of novel TB treatments that inhibit secretion via the ESX-3.
Item Metadata
Title |
Structural and functional characterization of the ESX-3 secretion system in mycobacteria
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Creator | |
Supervisor | |
Publisher |
University of British Columbia
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Date Issued |
2023
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Description |
Mycobacteria, including the pathogenic species Mycobacterium tuberculosis (Mtb), possess
a unique cell envelope structure that confers resistance to environmental stresses and antimicrobial
agents. Mtb, the causative agent of tuberculosis (TB), is a global health concern with increasing
drug resistance. The ESX-3 secretion system found in Mtb and other mycobacteria plays a crucial
role in the secretion of effector proteins that confer pathogenicity. This thesis focuses on studying
the ESX-3 secretion system in mycobacteria by: 1) determining the localization of the secreted
substrates PE5-PPE4 in M. smegmatis, and 2) characterizing the in vivo structure of the ESX-3
from Mtb. Briefly, the ESX-3 substrate PPE4 was found localized to the MOM of M. smegmatis,
and ESX-3 from Mtb was found to localize to the poles of M. marinum forming a putative trans envelope structure. Together, this research contributes to our understanding of the role of ESX-3 in
pathogenicity of mycobacteria and may inform the development of novel TB treatments that inhibit
secretion via the ESX-3.
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Genre | |
Type | |
Language |
eng
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Date Available |
2023-08-22
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0435528
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2023-11
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International