C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis

Patricia A. DiGiuseppe Champion; Sarah A. Stanley; Matthew M. Champion; Eric J. Brown; Jeffery S. Cox

doi:10.1126/science.1131167

C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis

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

Research output: Contribution to journal › Article › peer-review

185 Scopus citations

Abstract

Mycobacterium tuberculosis uses the ESK-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 ESK-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.

Original language	English
Pages (from-to)	1632-1636
Number of pages	5
Journal	Science
Volume	313
Issue number	5793
DOIs	https://doi.org/10.1126/science.1131167
State	Published - 15 Sep 2006
Externally published	Yes

Access to Document

10.1126/science.1131167

Cite this

@article{6c65619e38c54fbf94a12c8aa231304d,

title = "C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis",

abstract = "Mycobacterium tuberculosis uses the ESK-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 ESK-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.",

author = "\{DiGiuseppe Champion\}, \{Patricia A.\} and Stanley, \{Sarah A.\} and Champion, \{Matthew M.\} and Brown, \{Eric J.\} and Cox, \{Jeffery S.\}",

year = "2006",

month = sep,

day = "15",

doi = "10.1126/science.1131167",

language = "English",

volume = "313",

pages = "1632--1636",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5793",

}

TY - JOUR

T1 - C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis

AU - DiGiuseppe Champion, Patricia A.

AU - Stanley, Sarah A.

AU - Champion, Matthew M.

AU - Brown, Eric J.

AU - Cox, Jeffery S.

PY - 2006/9/15

Y1 - 2006/9/15

N2 - Mycobacterium tuberculosis uses the ESK-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 ESK-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.

AB - Mycobacterium tuberculosis uses the ESK-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 ESK-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.

UR - https://www.scopus.com/pages/publications/33748776564

U2 - 10.1126/science.1131167

DO - 10.1126/science.1131167

M3 - Article

C2 - 16973880

AN - SCOPUS:33748776564

SN - 0036-8075

VL - 313

SP - 1632

EP - 1636

JO - Science

JF - Science

IS - 5793

ER -

C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis

Abstract

Access to Document

Fingerprint

Cite this