Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: Characterization of the prototypic gene and its protein product, SET1

We report the discovery of a novel genetic locus within Staphylococcus aure us that encodes a cluster of at least five exotoxin-like proteins. Designat ed 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 pr oteins contain consensus sequences that are found in staphylococcal and str eptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, th e SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The pro totypic gene in this cluster, set1, has been cloned and expressed. Recombin ant SET1 stimulated the production of interleukin-1 beta, interleukin-6, an d tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. a ureus but not in the other staphylococcal species examined. Sequence analys is of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-f old difference in their cytokine-inducing potency. The distribution of alle lic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.