C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis |
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| Authors: | Champion Patricia A Digiuseppe Stanley Sarah A Champion Matthew M Brown Eric J Cox Jeffery S |
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| Affiliation: | Department of Microbiology and Immunology, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, CA 94143-2200, USA. |
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| 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. |
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