title: Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B.
abstract: We identified a novel pathogenicity island in Staphylococcus aureus which contains open reading frames (ORFs) similar to the exfoliative toxin (ET) gene, glutamyl endopeptidase gene, and edin-B gene in tandem and the phage resistance gene, flanked by hsdM, hsdS (restriction and modification system), and IS256. The protein encoded by the ET-like gene showed 40, 59, and 68% amino acid sequence identities with exfoliative toxin A (ETA), exfoliative toxin B (ETB), and Staphylococcus hyicus ETB (ShETB), respectively. When injected into neonatal mice, the recombinant protein derived from the ET-like gene induced exfoliation of the skin with loss of cell-to-cell adhesion in the upper part of the epidermis as observed in histological examinations, just as was found in neonatal mice injected with ETA or ETB. Western blot analysis indicated that the recombinant protein is serologically distinct from ETA and ETB. Therefore, the product encoded by this new ORF is a new ET member produced by S. aureus and is termed ETD. ETD did not induce blisters in 1-day-old chickens. In the skins of mice injected with ETD, cell surface staining of desmoglein 1 (Dsg1), a cadherin type cell-to-cell adhesion molecule in desmosomes, was abolished without affecting that of desmoglein 3 (Dsg3). Furthermore, in vitro incubation of the recombinant extracellular domains of Dsg1 and Dsg3 with the recombinant protein demonstrated that both mouse and human Dsg1, but not Dsg3, were directly cleaved in a dose-dependent manner. These results demonstrate that ETD and ETA induce blister formation by identical pathophysiological mechanisms. Clinical strains positive for edin-B were suggested to be clonally associated, and all edin-B-positive strains tested were positive for etd. Among 18 etd-positive strains, 12 produced ETD extracellularly. Interestingly, these strains are mainly isolated from other sources of infections and not from patients with bullous impetigo or staphylococcal scalded-skin syndrome. This strongly suggests that ETD might play a pathogenic role in a broader spectrum of bacterial infections than previously considered.
authors.affiliation: Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Kasumi 1-2-3, Minami-ku Hiroshima, Hiroshima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Nishifuji
authors.forename: Megumi
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fudaba
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.forename: Masaru
authors.initials: M
authors.lastname: Ohara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002645:Chickens; D004269:DNA, Bacterial / Q000235:genetics; D051183:Desmoglein 1; D051184:Desmoglein 3; D005083:Exfoliatins / Q000235:genetics* / Q000633:toxicity; D005798:Genes, Bacterial; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics; D013203:Staphylococcal Infections / Q000209:etiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D015820:Cadherins; D004269:DNA, Bacterial; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; D005083:Exfoliatins; C067120:epidermal cell differentiation inhibitor, Staphylococcus aureus; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase