Staphylococcus pseudintermedius exfoliative toxin EXI selectively digests canine desmoglein 1 and causes subcorneal clefts in canine epidermis

• Published in: Veterinary dermatology 2011-08, Vol.22 (4), p.319-326
• Main Authors: Iyori, Keita, Futagawa-Saito, Keiko, Hisatsune, Junzo, Yamamoto, Masahiko, Sekiguchi, Maiko, Ide, Kaori, Son, Won-Geun, Olivry, Thierry, Sugai, Motoyuki, Fukuyasu, Tsuguaki, Iwasaki, Toshiroh, Nishifuji, Koji
• Format: Article
• Language: English
• Subjects: Animals; Desmoglein 1 - metabolism; Dog Diseases - chemically induced; Dogs; Drug Eruptions - veterinary; Epidermis - drug effects; Escherichia coli; Exfoliatins - metabolism; Exfoliatins - toxicity; Gene Expression Regulation, Bacterial; Mice; Recombinant Proteins - metabolism; Staphylococcus; Staphylococcus - classification; Staphylococcus - metabolism
• ISSN: 0959-4493; 1365-3164
• DOI: 10.1111/j.1365-3164.2011.00952.x

Staphylococcal exfoliative toxins are known to digest desmoglein (Dsg) 1, a desmosomal cell–cell adhesion molecule, thus causing intraepidermal splitting in human bullous impetigo, staphylococcal scalded skin syndrome and swine exudative epidermitis. Recently, a novel exfoliative toxin gene (exi), whose sequence shares significant homology with previously identified exfoliative toxins, was isolated from Staphylococcus pseudintermedius. Little is known about the pathogenic involvement of this toxin in canine pustular diseases such as impetigo. The aim of this study was to determine whether EXI, the product of the exi gene, digests canine Dsg1 and causes intraepidermal splitting in canine skin. An exi gene was isolated from chromosomal DNA of an S. pseudintermedius strain obtained from a pustule of a dog with impetigo, and was used to produce a recombinant EXI by Escherichia coli expression. When purified recombinant EXI was injected intradermally into normal dogs, it caused the development of vesicles or erosions with superficial epidermal splitting. In addition, the EXI abolished immunofluorescence for Dsg1, but not for Dsg3, at the injection sites. Moreover, the EXI directly degraded baculovirus‐secreted recombinant extracellular domains of canine Dsg1, but not that of canine Dsg3, in vitro. The EXI also degraded mouse Dsg1α and swine Dsg1, but not human Dsg1, mouse Dsg1β and Dsg1γ. Conversely, recombinant SIET, previously designated as S. intermedius exfoliative toxin, did not cause intraepidermal splitting or degradation of any Dsgs. These findings indicate that EXI has a proteolytic activity that digests canine Dsg1, and this characteristic might be involved in the pathogenesis of intraepidermal splitting in canine impetigo. Résumé Les toxines exfoliatives staphylococciques sont connues pour digérer la desmogléine (Dsg) 1, molécule d’adhésion intercellulaire, entrainant ainsi un clivage intra épidermique dans l’impétigo bulleux de l’homme, le “staphylococcal scalded‐skin syndrome” et la dermatite exsudative porcine. Récemment, un nouveau gène de toxine exfoliative (exi), dont la séquence partage une homologie significative avec les toxines exfoliatives précédemment identifiées, a été isoléà partir de Staphylococcus pseudintermedius. Peu de choses sont connues sur le rôle pathogénique de cette toxine dans les maladies pustuleuses canines telle que l’impétigo. L’objectif de cette étude était de déterminer si EXI, le produit du gène exi, digère la Dsg1 ca