Staphylococcus aureus isolates carrying the genes that encode for Panton-Valentine leucocidin (PVL), a highly potent toxin, have been responsible for recent outbreaks of severe invasive disease in previously healthy children and adults in the United States of America and Europe. To determine the frequency of PVL-positive isolates sent to the Staphylococcus Reference Unit (United Kingdom) for epidemiological purposes, we tested 515 isolates of S. aureus, and 8 (1.6%) were positive for the PVL locus. A further 470 isolates were selected to explore the association of PVL-positive S. aureus with clinical disease. Of these, 23 (4.9%) were PVL positive and most were associated with skin and soft tissue infections (especially abscesses). The PVL genes were also detected in isolates responsible for community-acquired pneumonia, burn infections, bacteremia, and scalded skin syndrome. Genotyping by pulsed-field gel electrophoresis and multilocus sequence typing revealed that the PVL-positive isolates were from diverse genetic backgrounds, although one prevalent clone of 12 geographically dispersed methicillin-resistant S. aureus (MRSA) isolates was identified (ST80). All 12 isolates were stapylococcal cassette chromosome mec type IVc, had an agr3 allele, and shared a common toxin gene profile (sea-see, seg-sej, eta, etb, and tst negative but etd positive). ST80 strains with similar genetic characteristics have been responsible for community-acquired infections in France and Switzerland. The remaining PVL-positive isolates were mostly methicillin-sensitive S. aureus and belonged to 12 different sequence types, including ST22 and ST30, which are closely related to the most prevalent MRSA clones in United Kingdom hospitals, EMRSA-15 and EMRSA-16, respectively.Staphylococcus aureus is a very successful hospital and community-acquired pathogen. It causes a broad spectrum of disease, from mild skin infections to more serious invasive infections, including septicemia, pneumonia, endocarditis, and deep-seated abscesses. Pathogenicity is related to a number of virulence factors that allow it to adhere to surfaces, invade or avoid the immune system, and cause harmful toxic effects to the host. These factors include cell surface components (e.g., protein A, fibronectin-binding protein, collagen-binding protein, and clumping factor), and exoproteins (e.g., enterotoxins, exfoliatins, toxic shock syndrome toxin, and Panton-Valentine leucocidin [PVL]).PVL is a pore-forming cytotoxin that targets human and rabbit mononuclear and polymorphonuclear cells (37). When injected intradermally into rabbits, it induces severe inflammatory lesions, leading to capillary dilation, chemotaxis, polymorphonuclear karyorrhexis, and skin necrosis (44). Studies have shown that its toxic effect results from the synergistic action of two separate exoproteins, namely, LukS-PV and LukF-PV. These proteins are encoded by two contiguous and cotranscribed genes (lukS-PV and lukF-PV) (36), which are carried on temperate bacteriophages (20). Lysogenic conversion of...