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Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections.

Abstract
Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69) were analyzed with respect to virulence factor expression and cytotoxic or inflammatory effects on human cells and 3D skin tissue models. SDSE strains efficiently infected the 3D-skin model and severe tissue pathology, inflammatory responses and altered production of host structural framework proteins associated with epithelial barrier integrity were evident already at 8 hours post-infection. Invasive strains were significantly more cytotoxic towards keratinocytes and expressed higher Streptokinase and Streptolysin O (SLO) activities, as compared to non-invasive strains. The opposite was true for Streptolysin S (SLS). Fractionation and proteomic analysis of the cytotoxic fractions implicated SLO as a factor likely contributing to the keratinocyte cytotoxicity and tissue pathology. Analyses of patient tissue biopsies revealed massive bacterial load, high expression of slo, as well as immune cell infiltration and pro-inflammatory markers. Our findings suggest the contribution of SLO to epithelial cytotoxicity and tissue pathology in SDSE tissue infections.
AuthorsNikolai Siemens, Bård R Kittang, Bhavya Chakrakodi, Oddvar Oppegaard, Linda Johansson, Trond Bruun, Haima Mylvaganam, INFECT Study Group, Mattias Svensson, Steiner Skrede, Anna Norrby-Teglund
JournalScientific reports (Sci Rep) Vol. 5 Pg. 16945 (Nov 25 2015) ISSN: 2045-2322 [Electronic] England
PMID26601609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Proteins
  • Cytokines
  • HMGB1 Protein
  • Interleukin-8
  • Proteome
  • Streptolysins
  • Virulence Factors
  • streptolysin O
Topics
  • Bacterial Proteins (metabolism, toxicity)
  • Cell Culture Techniques
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Cytokines (analysis, metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • HMGB1 Protein (analysis)
  • Humans
  • Interleukin-8 (analysis)
  • Keratinocytes (cytology, metabolism)
  • Leukocytes, Mononuclear (cytology, metabolism)
  • Proteome (analysis)
  • Skin (metabolism, microbiology, pathology)
  • Soft Tissue Infections (microbiology, pathology)
  • Streptococcal Infections (microbiology, pathology)
  • Streptococcus (metabolism, pathogenicity)
  • Streptolysins (metabolism, toxicity)
  • Tandem Mass Spectrometry
  • Virulence Factors (metabolism, toxicity)

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