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Infection and Immunity, August 2000, p. 4407-4415, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identification of a Novel Gene Cluster Encoding Staphylococcal Exotoxin-Like Proteins: Characterization of the Prototypic Gene and Its Protein Product, SET1

Rachel J. Williams,1 John M. Ward,2 Brian Henderson,1 Stephen Poole,3 Bernard P. O'Hara,2 Michael Wilson,4 and Sean P. Nair1,*

Cellular Microbiology Research Group, Division of Surgical Sciences,1 Department of Biochemistry and Molecular Biology,2 and Microbiology Department, Eastman Dental Institute,4 University College London, London, and Division of Endocrinology, National Institute for Biological Standards and Control, Potters Bar,3 United Kingdom

Received 2 February 2000/Returned for modification 28 March 2000/Accepted 27 April 2000

We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The prototypic gene in this cluster, set1, has been cloned and expressed. Recombinant SET1 stimulated the production of interleukin-1beta , interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. aureus but not in the other staphylococcal species examined. Sequence analysis of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency. The distribution of allelic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.

* Corresponding author. Mailing address: Cellular Microbiology Research Group, Division of Surgical Sciences, Eastman Dental Institute, University College London, 256 Gray's Inn Rd., London WC1X 8LD, United Kingdom. Phone: 44 1719151118. Fax: 44 1719151259. E-mail: s.nair{at}eastman.ucl.ac.uk.

Infection and Immunity, August 2000, p. 4407-4415, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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