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

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)...

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Published in:	Scientific reports Vol. 5; no. 1; p. 16945
Main Authors:	Siemens, Nikolai, Kittang, Bård R., Chakrakodi, Bhavya, Oppegaard, Oddvar, Johansson, Linda, Bruun, Trond, Mylvaganam, Haima, Svensson, Mattias, Skrede, Steiner, Norrby-Teglund, Anna
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 25-11-2015 Nature Publishing Group
Subjects:	631/326/421 692/699/4033 Bacterial Proteins - metabolism Bacterial Proteins - toxicity Cell Culture Techniques Cell Proliferation - drug effects Cell Survival - drug effects Cells, Cultured Cytokines - analysis Cytokines - metabolism Enzyme-Linked Immunosorbent Assay HMGB1 Protein - analysis Humanities and Social Sciences Humans Interleukin-8 - analysis Keratinocytes - cytology Keratinocytes - metabolism Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - metabolism Medicin och hälsovetenskap multidisciplinary Proteome - analysis Science Skin - metabolism Skin - microbiology Skin - pathology Soft Tissue Infections - microbiology Soft Tissue Infections - pathology Streptococcal Infections - microbiology Streptococcal Infections - pathology Streptococcus - metabolism Streptococcus - pathogenicity Streptolysins - metabolism Streptolysins - toxicity Tandem Mass Spectrometry Virulence Factors - metabolism Virulence Factors - toxicity
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 A comprehensive list of authors and affiliations appear at the end of the paper.
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep16945