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Science 15 September 2006:
Vol. 313. no. 5793, pp. 1632 - 1636
DOI: 10.1126/science.1131167
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Reports

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

Patricia A. DiGiuseppe Champion,1,2 Sarah A. Stanley,1,2 Matthew M. Champion,3 Eric J. Brown,2 Jeffery S. Cox1,2*

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.

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.

* To whom correspondence should be addressed. E-mail: Jeffery.Cox{at}ucsf.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)