Deletion of RD1 from Mycobacterium tuberculosis Mimics Bacille Calmette-Guérin Attenuation
Kaeryn N. Lewis,Reiling Liao,Kristi M. Guinn,Mark J. Hickey,Sherilyn Smith,Marcel A. Behr,David R. Sherman +6 more
TLDR
It was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation.Abstract:
The tuberculosis (TB) vaccine bacille Calmette-Guerin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5-kb region are of unknown function, although they include the TB-specific immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections of the human macrophage-like cell line THP-1, human peripheral blood monocyte-derived macrophages, and C57BL/6 mice. In each of these systems, the H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar to BCG controls. Therefore, it was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation.read more
Citations
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Genetic requirements for mycobacterial survival during infection
TL;DR: A surprisingly large fraction of these genes are unique to mycobacteria and closely related species, indicating that many of the strategies used by this unusual group of organisms are fundamentally different from other pathogens.
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Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence
TL;DR: There is more TB than ever before, requiring new vaccines and drugs and more specific and rapid diagnostics, and researchers are utilizing information obtained from the complete sequence of the M. tuberculosis genome and from new genetic and physiological methods to identify targets in M. TB that will aid in the development of these sorely needed antitubercular agents.
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M. tuberculosis and M. leprae Translocate from the Phagolysosome to the Cytosol in Myeloid Cells
Nicole N. van der Wel,David L. Hava,Diane Houben,Donna M. Fluitsma,Maaike van Zon,Jason Pierson,Michael B. Brenner,Peter J. Peters +7 more
TL;DR: It is shown that lysosomes rapidly fuse with the virulent M. tuberculosis- and M. leprae-containing phagosomes of human monocyte-derived dendritic cells and macrophages, revealing a mechanism for MHC-based antigen presentation that is lacking in current vaccine strains.
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The primary mechanism of attenuation of bacillus Calmette–Guérin is a loss of secreted lytic function required for invasion of lung interstitial tissue
Tsungda Hsu,Suzanne M. Hingley-Wilson,Bing Chen,Mei Chen,Annie Z. Dai,Paul M. Morin,Carolyn Marks,Jeevan Padiyar,Celia W. Goulding,Mari Gingery,David Eisenberg,Robert G. Russell,Steven C. Derrick,Frank M. Collins,Sheldon L. Morris,C. Harold King,William R. Jacobs +16 more
TL;DR: The primary attenuating mechanism of bacillus Calmette–Guérin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness.
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Type VII secretion — mycobacteria show the way
Abdallah M. Abdallah,Nicolaas C Gey van Pittius,Patricia A. DiGiuseppe Champion,Jeffery S. Cox,Joen Luirink,Christina M. J. E. Vandenbroucke-Grauls,Ben J. Appelmelk,Wilbert Bitter +7 more
TL;DR: Given the unique composition of this secretion system, and its general importance, it is proposed that, in line with the accepted nomenclature, it should be called type VII secretion.
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Book
Tuberculosis Pathogenesis, Protection, and Control
TL;DR: The history of clinical tuberculosis, Epidemiology of tuberculosis, and molecular approaches to diagnosis and new approaches to vaccines for tuberculosis.
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