PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence.

Bibliographic Details
Title: PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence.
Authors: Jesús Gonzalo-Asensio, Serge Mostowy, Jose Harders-Westerveen, Kris Huygen, Rogelio Hernández-Pando, Jelle Thole, Marcel Behr, Brigitte Gicquel, Carlos Martín
Source: PLoS ONE, Vol 3, Iss 10, p e3496 (2008)
Publisher Information: Public Library of Science (PLoS), 2008.
Publication Year: 2008
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: Inactivation of the transcriptional regulator PhoP results in Mycobacterium tuberculosis attenuation. Preclinical testing has shown that attenuated M. tuberculosis phoP mutants hold promise as safe and effective live vaccine candidates. We focused this study to decipher the virulence networks regulated by PhoP. A combined transcriptomic and proteomic analysis revealed that PhoP controls a variety of functions including: hypoxia response through DosR crosstalking, respiratory metabolism, secretion of the major T-cell antigen ESAT-6, stress response, synthesis of pathogenic lipids and the M. tuberculosis persistence through transcriptional regulation of the enzyme isocitrate lyase. We also demonstrate that the M. tuberculosis phoP mutant SO2 exhibits an antigenic capacity similar to that of the BCG vaccine. Finally, we provide evidence that the SO2 mutant persists better in mouse organs than BCG. Altogether, these findings indicate that PhoP orchestrates a variety of functions implicated in M. tuberculosis virulence and persistence, making phoP mutants promising vaccine candidates.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC2566814?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0003496
Access URL: https://doaj.org/article/acf078ffa7584179b0b1223916c2ab17
Accession Number: edsdoj.f078ffa7584179b0b1223916c2ab17
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0003496
Published in:PLoS ONE
Language:English