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ESX-1: A novel alternative secretion...
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Stanley, Sarah A.
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ESX-1: A novel alternative secretion system in Mycobacterium tuberculosis that mediates the host-pathogen interaction.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
ESX-1: A novel alternative secretion system in Mycobacterium tuberculosis that mediates the host-pathogen interaction./
Author:
Stanley, Sarah A.
Description:
144 p.
Notes:
Adviser: Jeffery Cox.
Contained By:
Dissertation Abstracts International67-08B.
Subject:
Biology, Microbiology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3229284
ISBN:
9780542829062
ESX-1: A novel alternative secretion system in Mycobacterium tuberculosis that mediates the host-pathogen interaction.
Stanley, Sarah A.
ESX-1: A novel alternative secretion system in Mycobacterium tuberculosis that mediates the host-pathogen interaction.
- 144 p.
Adviser: Jeffery Cox.
Thesis (Ph.D.)--University of California, San Francisco, 2006.
Mycobacterium tuberculosis is one of the world's most successful pathogens, infecting approximately one-third of humanity. This remarkable bacterium has infected human beings for millennia, and has evolved mechanisms for the manipulation of host biology to create an optimal environment for bacterial survival and growth. Here we describe the identification and characterization of ESX-1, the first alternative secretion system identified in M. tuberculosis, and show its fundamental importance for virulence. We have identified three genes, Rv3870, Rv3871, and Rv3877, that encode components of the ESX-1 secretion system, which functions to secrete ESAT-6 and CFP-10, proteins with dual functions as immunodominant antigens and virulence factors. Components and substrates of ESX-1 are required for full virulence of M. tuberculosis in both mice and macrophages. The ESX-1 secretion system functions to subvert host cell biology, and is required for the suppression of Interleukin-12 (IL-12) and Tumor Necrosis Factor-alpha (TNF-alpha). ESX-1 is also required for the induction, both in vivo and in vitro, of type I Interferons (IFNs), cytokines usually associated with an anti-viral immune response. We show that the induction of type I IFNs may be a pathogenic strategy that enhances virulence of M. tuberculosis. We also examine the role of the ESAT-6 and CFP-10 in the protective immune response in M. tuberculosis. We find that restoration of a functional ESX-1 system to the live attenuated vaccine strain mycobacterium Bacille Calmette-Guerin results in an increase in immunogenicity of this strain, which may lead to the development of more a more effective vaccine. These studies identify ESX-1 mediated secretion of ESAT-6 and CFP-10 to one of the most important pathways identified in M. tuberculosis, both for virulence of the organism and for induction of the protective immune response to infection, and begin to describe the mechanisms by which ESX-1 secretion regulates host biology and the outcome of infection.
ISBN: 9780542829062Subjects--Topical Terms:
1017734
Biology, Microbiology.
ESX-1: A novel alternative secretion system in Mycobacterium tuberculosis that mediates the host-pathogen interaction.
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Source: Dissertation Abstracts International, Volume: 67-08, Section: B, page: 4241.
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Thesis (Ph.D.)--University of California, San Francisco, 2006.
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Mycobacterium tuberculosis is one of the world's most successful pathogens, infecting approximately one-third of humanity. This remarkable bacterium has infected human beings for millennia, and has evolved mechanisms for the manipulation of host biology to create an optimal environment for bacterial survival and growth. Here we describe the identification and characterization of ESX-1, the first alternative secretion system identified in M. tuberculosis, and show its fundamental importance for virulence. We have identified three genes, Rv3870, Rv3871, and Rv3877, that encode components of the ESX-1 secretion system, which functions to secrete ESAT-6 and CFP-10, proteins with dual functions as immunodominant antigens and virulence factors. Components and substrates of ESX-1 are required for full virulence of M. tuberculosis in both mice and macrophages. The ESX-1 secretion system functions to subvert host cell biology, and is required for the suppression of Interleukin-12 (IL-12) and Tumor Necrosis Factor-alpha (TNF-alpha). ESX-1 is also required for the induction, both in vivo and in vitro, of type I Interferons (IFNs), cytokines usually associated with an anti-viral immune response. We show that the induction of type I IFNs may be a pathogenic strategy that enhances virulence of M. tuberculosis. We also examine the role of the ESAT-6 and CFP-10 in the protective immune response in M. tuberculosis. We find that restoration of a functional ESX-1 system to the live attenuated vaccine strain mycobacterium Bacille Calmette-Guerin results in an increase in immunogenicity of this strain, which may lead to the development of more a more effective vaccine. These studies identify ESX-1 mediated secretion of ESAT-6 and CFP-10 to one of the most important pathways identified in M. tuberculosis, both for virulence of the organism and for induction of the protective immune response to infection, and begin to describe the mechanisms by which ESX-1 secretion regulates host biology and the outcome of infection.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3229284
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