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

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Abstract
We report the discovery of a novel genetic locus withinStaphylococcus aureusthat encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1toset5), 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-1β, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed thatset1was distributed among other strains ofS. aureusbut not in the other staphylococcal species examined. Sequence analysis of theset1genes 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 thesetgenes among strains ofS. aureusmay contribute to differences in the pathogenic potential of this bacterium.

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