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.
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-1
, 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.
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