Streptococcal Cysteine Protease-Mediated Cleavage of Desmogleins Is Involved in the Pathogenesis of Cutaneous Infection

Front Cell Infect Microbiol. 2018 Jan 24:8:10. doi: 10.3389/fcimb.2018.00010. eCollection 2018.

Abstract

Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain. Furthermore, immunohistological analysis indicated cleavage of desmogleins that developed around the invasion site of the wild-type strain. In contrast, the speB mutant was preferentially found on the epidermis surface layer. Taken together, our findings provide evidence that SpeB-mediated degradation of desmosomes has a pathogenic role in development of S. pyogenes cutaneous infection.

Keywords: SpeB; Streptococcus pyogenes; cutaneous infection; desmogleins; epidermal barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysteine Proteases / genetics
  • Cysteine Proteases / metabolism*
  • Desmogleins / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mutation
  • Proteolysis
  • Skin Diseases, Bacterial / metabolism*
  • Skin Diseases, Bacterial / microbiology*
  • Streptococcal Infections / metabolism*
  • Streptococcal Infections / microbiology*
  • Streptococcus pyogenes / enzymology*
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / pathogenicity
  • Virulence

Substances

  • Desmogleins
  • Cysteine Proteases