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Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound-associated extracellular matrix: implications for cancer therapy.

Authors
  • McNitt, Dudley H1
  • Choi, Soo Jeon1
  • Allen, Jessica L2
  • Hames, River A2
  • Weed, Scott A2
  • Van De Water, Livingston3
  • Berisio, Rita4
  • Lukomski, Slawomir1
  • 1 Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA.
  • 2 Department of Biochemistry, Program in Cancer Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA.
  • 3 Departments of Surgery and Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY, USA.
  • 4 Institute of Biostructures and Bioimaging, National Research Council, Naples, Italy. , (Italy)
Type
Published Article
Journal
Molecular Microbiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2019
Volume
112
Issue
3
Pages
800–819
Identifiers
DOI: 10.1111/mmi.14317
PMID: 31145503
Source
Medline
Language
English
License
Unknown

Abstract

The human-adapted pathogen group A Streptococcus (GAS) utilizes wounds as portals of entry into host tissue, wherein surface adhesins interact with the extracellular matrix, enabling bacterial colonization. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin of GAS that selectively binds to two fibronectin type III (FnIII) repeats within cellular fibronectin, specifically the alternatively spliced extra domains A and B, and the FnIII repeats within tenascin-C. Binding to FnIII repeats was mediated through conserved structural determinants present within the Scl1 globular domain and facilitated GAS adherence and biofilm formation. Isoforms of cellular fibronectin that contain extra domains A and B, as well as tenascin-C, are present for several days in the wound extracellular matrix. Scl1-FnIII binding is therefore an example of GAS adaptation to the host's wound environment. Similarly, cellular fibronectin isoforms and tenascin-C are present in the tumor microenvironment. Consistent with this, FnIII repeats mediate GAS attachment to and enhancement of biofilm formation on matrices deposited by cancer-associated fibroblasts and osteosarcoma cells. These data collectively support the premise for utilization of the Scl1-FnIII interaction as a novel method of anti-neoplastic targeting in the tumor microenvironment. © 2019 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

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