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Science 30 July 1999:
Vol. 285. no. 5428, pp. 760 - 763
DOI: 10.1126/science.285.5428.760
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Reports

Staphylococcus aureus Sortase, an Enzyme that Anchors Surface Proteins to the Cell Wall

Sarkis K. Mazmanian, Gwen Liu, Hung Ton-That, Olaf Schneewind *

Surface proteins of Gram-positive bacteria are linked to the bacterial cell wall by a mechanism that involves cleavage of a conserved Leu-Pro-X-Thr-Gly (LPXTG) motif and that occurs during assembly of the peptidoglycan cell wall. A Staphylococcus aureus mutant defective in the anchoring of surface proteins was isolated and shown to carry a mutation in the srtA gene. Overexpression of srtA increased the rate of surface protein anchoring, and homologs of srtA were found in other pathogenic Gram-positive bacteria. The protein specified by srtA, sortase, may be a useful target for the development of new antimicrobial drugs.

Department of Microbiology and Immunology, UCLA School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
*   To whom correspondence should be addressed. E-mail: olafs{at}ucla.edu

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Critical Reviews in Oral Biology & Medicine 12, 101-115
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Streptococcus thermophilus Cell Wall-Anchored Proteinase: Release, Purification, and Biochemical and Genetic Characterization.
M. D. Fernandez-Espla, P. Garault, V. Monnet, and F. Rul (2000)
Appl. Envir. Microbiol. 66, 4772-4778
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Protein A is the von Willebrand factor binding protein on Staphylococcus aureus.
J. Hartleib, N. Kohler, R. B. Dickinson, G. S. Chhatwal, J. J. Sixma, O. M. Hartford, T. J. Foster, G. Peters, B. E. Kehrel, and M. Herrmann (2000)
Blood 96, 2149-2156
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Signal Peptide-Dependent Protein Transport in Bacillus subtilis: a Genome-Based Survey of the Secretome.
H. Tjalsma, A. Bolhuis, J. D. H. Jongbloed, S. Bron, and J. M. van Dijl (2000)
Microbiol. Mol. Biol. Rev. 64, 515-547
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Sortase, a universal target for therapeutic agents against Gram-positive bacteria?.
P. Cossart and R. Jonquieres (2000)
PNAS 97, 5013-5015
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The Fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus Is a Bifunctional Protein That Also Binds to Fibrinogen.
E. R. Wann, S. Gurusiddappa, and M. Hook (2000)
J. Biol. Chem. 275, 13863-13871
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Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus. SORTASE CATALYZED IN VITRO TRANSPEPTIDATION REACTION USING LPXTG PEPTIDE AND NH2-GLY3 SUBSTRATES.
H. Ton-That, S. K. Mazmanian, K. F. Faull, and O. Schneewind (2000)
J. Biol. Chem. 275, 9876-9881
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Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif.
H. Ton-That, G. Liu, S. K. Mazmanian, K. F. Faull, and O. Schneewind (1999)
PNAS 96, 12424-12429
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Identification of Residues in the Staphylococcus aureus Fibrinogen-binding MSCRAMM Clumping Factor A (ClfA) That Are Important for Ligand Binding.
O. M. Hartford, E. R. Wann, M. Hook, and T. J. Foster (2001)
J. Biol. Chem. 276, 2466-2473
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Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus. CYSTEINE 184 AND HISTIDINE 120 OF SORTASE FORM A THIOLATE-IMIDAZOLIUM ION PAIR FOR CATALYSIS.
H. Ton-That, S. K. Mazmanian, L. Alksne, and O. Schneewind (2002)
J. Biol. Chem. 277, 7447-7452
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An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis.
S. K. Mazmanian, H. Ton-That, K. Su, and O. Schneewind (2002)
PNAS 99, 2293-2298
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From the Cover: Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections.
S. K. Mazmanian, G. Liu, E. R. Jensen, E. Lenoy, and O. Schneewind (2000)
PNAS 97, 5510-5515
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