Home LiteratureArticle Details
PMID: 15657139 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 4 ·2005-01-25 ·Pages 1169-74

Burts ML, Williams WA, DeBord K, Missiakas DM

Abstract

Mycobacterium tuberculosis secretes ESAT-6, a virulence factor that triggers cell-mediated immune responses and IFN-gamma production during tuberculosis. ESAT-6 is transported across the bacterial envelope by a specialized secretion system with a FSD (FtsK-SpoIIIE domain) membrane protein. Although the presence of ESAT-6-like genes has been identified in the genomes of other microbes, the possibility that they may encode general virulence functions has hitherto not been addressed. Herein we show that the human pathogen Staphylococcus aureus secretes EsxA and EsxB, ESAT-6-like proteins, across the bacterial envelope. Staphylococcal esxA and esxB are clustered with six other genes and some of these are required for synthesis or secretion of EsxA and EsxB. Mutants that failed to secrete EsxA and EsxB displayed defects in the pathogenesis of S. aureus murine abscesses, suggesting that this specialized secretion system may be a general strategy of human bacterial pathogenesis.

MeSH Terms
Abscess/etiology Amino Acid Sequence Animals Antigens, Bacterial/analysis,physiology Bacterial Proteins Female Mice Mice, Inbred BALB C Molecular Sequence Data Phenotype Staphylococcal Infections/etiology Staphylococcus aureus/pathogenicity Virulence Factors/physiology
Chemicals
Antigens, Bacterial Bacterial Proteins ESAT-6 protein, Mycobacterium tuberculosis Virulence Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Burts Monica L
Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
Williams Wade A
DeBord Kristin
Missiakas Dominique M
References (48)
48 references, click to expand
  1. Virulence of Staphylococcus aureus mutants altered in type 5 capsule production.
    Infect Immun. 1991 Mar;59(3):1008-14 PMID: 1847696
  2. Bacillus subtilis operon encoding a membrane receptor for bacteriophage SPP1.
    J Bacteriol. 2004 Dec;186(24):8337-46 PMID: 15576783
  3. Sorting of protein A to the staphylococcal cell wall.
    Cell. 1992 Jul 24;70(2):267-81 PMID: 1638631
  4. A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity.
    J Exp Med. 1992 Aug 1;176(2):415-26 PMID: 1500854
  5. Structure of the cell wall anchor of surface proteins in Staphylococcus aureus.
    Science. 1995 Apr 7;268(5207):103-6 PMID: 7701329
  6. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis.
    Infect Immun. 1995 May;63(5):1710-7 PMID: 7729876
  7. Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities.
    Infect Immun. 1995 Oct;63(10):4121-9 PMID: 7558328
  8. Evidence for occurrence of the ESAT-6 protein in Mycobacterium tuberculosis and virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG.
    Infect Immun. 1996 Jan;64(1):16-22 PMID: 8557334
  9. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis.
    J Bacteriol. 1996 Mar;178(5):1274-82 PMID: 8631702
  10. Physical mapping of Mycobacterium bovis BCG pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from M. bovis.
    Microbiology. 1996 Nov;142 ( Pt 11):3135-45 PMID: 8969511
  11. A 12 kb nucleotide sequence containing the alanine dehydrogenase gene at 279 degrees on the Bacillus subtilis chromosome.
    Microbiology. 1997 May;143 ( Pt 5):1489-91 PMID: 9168598
  12. Staphylococcus aureus: a well-armed pathogen.
    Clin Infect Dis. 1998 May;26(5):1179-81 PMID: 9597249
  13. Exotoxins of Staphylococcus aureus.
    Clin Microbiol Rev. 2000 Jan;13(1):16-34, table of contents PMID: 10627489
  14. Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5510-5 PMID: 10805806
  15. Staphylococcus aureus bacteremia--consider the source.
    N Engl J Med. 2001 Jan 4;344(1):55-6 PMID: 11136962
  16. Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria.
    Cell. 2001 Jan 12;104(1):143-52 PMID: 11163247
  17. Whole genome sequencing of meticillin-resistant Staphylococcus aureus.
    Lancet. 2001 Apr 21;357(9264):1225-40 PMID: 11418146
  18. The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria.
    Genome Biol. 2001;2(10):RESEARCH0044 PMID: 11597336
  19. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients.
    Lancet. 2002 Mar 2;359(9308):753-9 PMID: 11888586
  20. Anchorless adhesins and invasins of Gram-positive bacteria: a new class of virulence factors.
    Trends Microbiol. 2002 May;10(5):205-8 PMID: 11973142
  21. The ESAT-6/WXG100 superfamily -- and a new Gram-positive secretion system?
    Trends Microbiol. 2002 May;10(5):209-12 PMID: 11973144
  22. On the role of Staphylococcus aureus sortase and sortase-catalyzed surface protein anchoring in murine septic arthritis.
    J Infect Dis. 2002 May 15;185(10):1417-24 PMID: 11992276
  23. Conclusive evidence that the major T-cell antigens of the Mycobacterium tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6*CFP-10 complex. Implications for pathogenesis and virulence.
    J Biol Chem. 2002 Jun 14;277(24):21598-603 PMID: 11940590
  24. Type iii protein secretion in yersinia species.
    Annu Rev Cell Dev Biol. 2002;18:107-33 PMID: 12142275
  25. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti.
    Mol Microbiol. 2002 Nov;46(3):709-17 PMID: 12410828
  26. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis.
    Nat Med. 2003 May;9(5):533-9 PMID: 12692540
  27. Autoinduction and signal transduction in the regulation of staphylococcal virulence.
    Mol Microbiol. 2003 Jun;48(6):1429-49 PMID: 12791129
  28. The Bacillus cereus bceT enterotoxin sequence reappraised.
    FEMS Microbiol Lett. 2003 Jun 6;223(1):21-4 PMID: 12798995
  29. PSORT-B: Improving protein subcellular localization prediction for Gram-negative bacteria.
    Nucleic Acids Res. 2003 Jul 1;31(13):3613-7 PMID: 12824378
  30. The role of Staphylococcus aureus sortase A and sortase B in murine arthritis.
    Microbes Infect. 2003 Jul;5(9):775-80 PMID: 12850203
  31. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12420-5 PMID: 14557547
  32. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13001-6 PMID: 14557536
  33. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus.
    Science. 2003 Nov 28;302(5650):1569-71 PMID: 14645850
  34. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis.
    Mol Microbiol. 2004 Jan;51(2):359-70 PMID: 14756778
  35. Protein-protein interactions of proteins from the ESAT-6 family of Mycobacterium tuberculosis.
    J Bacteriol. 2004 Apr;186(8):2487-91 PMID: 15060053
  36. A microdomain for protein secretion in Gram-positive bacteria.
    Science. 2004 Jun 4;304(5676):1513-5 PMID: 15178803
  37. Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing.
    Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12312-7 PMID: 15304642
  38. Subcellular sites for bacterial protein export.
    Mol Microbiol. 2004 Sep;53(6):1583-99 PMID: 15341641
  39. Virulence of Staphylococcus aureus in a mouse mastitis model: studies of alpha hemolysin, coagulase, and protein A as possible virulence determinants with protoplast fusion and gene cloning.
    Infect Immun. 1985 Sep;49(3):765-9 PMID: 4040889
  40. Regulation of exoprotein gene expression in Staphylococcus aureus by agar.
    Mol Gen Genet. 1986 Jan;202(1):58-61 PMID: 3007938
  41. Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement.
    Infect Immun. 1987 Dec;55(12):3103-10 PMID: 3679545
  42. Inactivation of the alpha-haemolysin gene of Staphylococcus aureus 8325-4 by site-directed mutagenesis and studies on the expression of its haemolysins.
    Microb Pathog. 1986 Apr;1(2):125-38 PMID: 3508485
  43. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.
    Nature. 1998 Jun 11;393(6685):537-44 PMID: 9634230
  44. Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope.
    Microbiol Mol Biol Rev. 1999 Mar;63(1):174-229 PMID: 10066836
  45. Type III secretion machines: bacterial devices for protein delivery into host cells.
    Science. 1999 May 21;284(5418):1322-8 PMID: 10334981
  46. Staphylococcal coagulase; mode of action and antigenicity.
    J Gen Microbiol. 1952 Feb;6(1-2):95-107 PMID: 14927856
  47. LYSOSTAPHIN: A NEW BACTERIOLYTIC AGENT FOR THE STAPHYLOCOCCUS.
    Proc Natl Acad Sci U S A. 1964 Mar;51:414-21 PMID: 14171453
  48. Alpha-toxin of Staphylococcus aureus.
    Microbiol Rev. 1991 Dec;55(4):733-51 PMID: 1779933
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0405620102
Published
2005-01-25
Epub
2005-00-18
Pages
1169-74
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC545836
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0405620102 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2