Characterization and Expression Analysis of Staphylococcus aureus Pathogenicity Island 3

Abstract

We describe the complete sequence of the 15.9-kb staphylococcal pathogenicity island 3 encoding staphylococcal enterotoxin serotypes B, K, and Q. The island, which meets the generally accepted definition of pathogenicity islands, contains 24 open reading frames potentially encoding proteins of more than 50 amino acids, including an apparently functional integrase. The element is bordered by two 17-bp direct repeats identical to those found flanking staphylococcal pathogenicity island 1. The island has extensive regions of homology to previously described pathogenicity islands, particularly staphylococcal pathogenicity islands 1 and bov. The expression of 22 of the 24 open reading frames contained on staphylococcal pathogenicity island 3 was detected either in vitro during growth in a laboratory medium or serum or in vivo in a rabbit model of toxic shock syndrome using DNA microarrays. The effect of oxygen tension on staphylococcal pathogenicity island 3 gene expression was also examined. By comparison with the known staphylococcal pathogenicity islands in the context of gene expression described here, we propose a model of pathogenicity island origin and evolution involving specialized transduction events and addition, deletion, or recombination of pathogenicity island “modules.” We describe the complete sequence of the 15.9-kb staphylococcal pathogenicity island 3 encoding staphylococcal enterotoxin serotypes B, K, and Q. The island, which meets the generally accepted definition of pathogenicity islands, contains 24 open reading frames potentially encoding proteins of more than 50 amino acids, including an apparently functional integrase. The element is bordered by two 17-bp direct repeats identical to those found flanking staphylococcal pathogenicity island 1. The island has extensive regions of homology to previously described pathogenicity islands, particularly staphylococcal pathogenicity islands 1 and bov. The expression of 22 of the 24 open reading frames contained on staphylococcal pathogenicity island 3 was detected either in vitro during growth in a laboratory medium or serum or in vivo in a rabbit model of toxic shock syndrome using DNA microarrays. The effect of oxygen tension on staphylococcal pathogenicity island 3 gene expression was also examined. By comparison with the known staphylococcal pathogenicity islands in the context of gene expression described here, we propose a model of pathogenicity island origin and evolution involving specialized transduction events and addition, deletion, or recombination of pathogenicity island “modules.” toxic shock syndrome staphylococcal pathogenicity island toxic shock syndrome toxin 1 open reading frame Todd-Hewitt staphylococcal enterotoxin Staphylococcus aureus is a leading etiologic agent of both nosocomial and community-acquired infections worldwide. These infections range from fairly benign cutaneous infections, such as furuncles, to potentially fatal diseases, including endocarditis and toxic shock syndrome (TSS)1(reviewed in Ref. 1.Tenover F.C. Gaynes R.P. Fischetti V.A. Novick R.P. Ferretti J.J. Portnoy D.A. Rood J.I. Gram-positive Pathogens. ASM Press, Washington, D. C.2000: 414-421Google Scholar). Its ability to cause this range of disease is due in part to its elaboration of a vast array of both cell surface-associated and secreted virulence factors. Among the secreted factors are the pyrogenic toxin superantigens that have the ability to activate large populations (10–50%) of T lymphocytes in a manner specific to the variable region of the β-chain of the T-cell receptor (2.Marrack P. Kappler J. Science. 1990; 248: 705-711Crossref PubMed Scopus (1210) Google Scholar). The ensuing massive cytokine release results in the symptoms of TSS, including fever, hypotension, rash, vomiting, diarrhea, multiple organ failure, disseminated intravascular coagulation, and desquamation. The staphylococcal enterotoxins (SEs), members of the superantigen family, are associated w