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

Abstract

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.

• Authors: Keita Iyori, Keiko Futagawa-Saito, Junzo Hisatsune, Masahiko Yamamoto, Maiko Sekiguchi, Kaori Ide, Won-Geun Son, Thierry Olivry, Motoyuki Sugai, Tsuguaki Fukuyasu, Toshiroh Iwasaki, Koji Nishifuji
• Journal: Veterinary dermatology (Vet Dermatol) Vol. 22 Issue 4 Pg. 319-26 (Aug 2011) ISSN: 1365-3164 [Electronic] England
• PMID: 21410798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

Chemical References

• Desmoglein 1
• Exfoliatins
• Recombinant Proteins

Topics

• Animals
• Desmoglein 1 (metabolism)
• Dog Diseases (chemically induced)
• Dogs
• Drug Eruptions (veterinary)
• Epidermis (drug effects)
• Exfoliatins (metabolism, toxicity)
• Gene Expression Regulation, Bacterial
• Mice
• Recombinant Proteins (metabolism)
• Staphylococcus (classification, metabolism)