PhoP: A Missing Piece in the Intricate Puzzle of Mycobacterium tuberculosis Virulence

作者：Gonzalo Asensio Jesus^*; Mostowy Serge; Harders Westerveen Jose; Huygen Kris; Hernandez Pando Rogelio; Thole Jelle; Behr Marcel; Gicquel Brigitte; Martin Carlos

来源：PLos One, 2008, 3(10): e3496.

DOI：10.1371/journal.pone.0003496

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.

• 出版日期2008-10-23
• 单位河北医科大学