C-Terminal Signal Sequence Promotes Virulence Factor Secretion in Mycobacterium tuberculosis-Reference-Cited by-同舟云学术

C-Terminal Signal Sequence Promotes Virulence Factor Secretion in Mycobacterium tuberculosis

Published:2006-09-15 Issue:5793 Volume:313 Page:1632-1636
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Champion Patricia A. DiGiuseppe¹²³,Stanley Sarah A.¹²³,Champion Matthew M.¹²³,Brown Eric J.¹²³,Cox Jeffery S.¹²³

Affiliation:

1. Department of Microbiology and Immunology, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, CA 94143–2200, USA.

2. Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, CA 94143–2200, USA.

3. Applied Biosystems, 353 Hatch Drive, Foster City, CA 94404, USA.

Abstract

Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from M. tuberculosis cells, demonstrating that this ESX-1 signal is portable.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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