A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis.
Tuberculosis is a chronic infectious disease caused by bacteria of the Mycobacterium tuberculosis complex. One of the major contributors to virulence and intercellular spread of M. tuberculosis is the ESAT-6 secretion system 1 (ESX-1) that has been lost by the live vaccines Mycobacterium bovis BCG (Bacille Calmette Guérin) and Mycobacterium microti as a result of independent deletions. ESX-1 consists of at least 10 genes (Rv3868-Rv3877) encoding the T-cell antigens ESAT-6 and CFP-10 as well as AAA-ATPases, chaperones, and membrane proteins which probably form a novel export system. To better understand the mode of action of the ESX-1 proteins, as a prelude to drug development, we examined systematically the interactions between the various proteins using the two-hybrid system in Saccharomyces cerevisiae. Interestingly, ESAT-6 and CFP-10 formed both hetero- and homodimers. Moreover, Rv3866, Rv3868, and CFP-10 interacted with Rv3873 which also homodimerized. The data were summarized in a protein linkage map that is consistent with the model for the secretion apparatus and can be used as a basis to identify inhibitors of specific interactions.
Teutschbein
Janka
J
Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research - Hans-Knöll-Institute, Germany.
Schumann
Gisbert
G
Möllmann
Ute
U
Grabley
Susanne
S
Cole
Stewart T
ST
Munder
Thomas
T
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D025941:Protein Interaction Mapping; D020798:Two-Hybrid System Techniques
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis