Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections

Copyright © 2020 American Chemical Society. Group A Streptococcus (GAS) displays cell-surface proteins that resemble human collagen. We find that a fluorophore-labeled collagen mimetic peptide (CMP) labels GAS cells but not Escherichia coli or Bacillus subtilis cells, which lack such proteins. The C...

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Main Authors: Ellison, Aubrey J, Dempwolff, Felix, Kearns, Daniel B, Raines, Ronald T
Format: Article
Language:English
Published: American Chemical Society (ACS) 2021
Online Access:https://hdl.handle.net/1721.1/132552
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author Ellison, Aubrey J
Dempwolff, Felix
Kearns, Daniel B
Raines, Ronald T
author_facet Ellison, Aubrey J
Dempwolff, Felix
Kearns, Daniel B
Raines, Ronald T
author_sort Ellison, Aubrey J
collection MIT
description Copyright © 2020 American Chemical Society. Group A Streptococcus (GAS) displays cell-surface proteins that resemble human collagen. We find that a fluorophore-labeled collagen mimetic peptide (CMP) labels GAS cells but not Escherichia coli or Bacillus subtilis cells, which lack such proteins. The CMP likely engages in a heterotrimeric helix with endogenous collagen, as the nonnatural d enantiomer of the CMP does not label GAS cells. To identify a molecular target, we used reverse genetics to "knock-in"the GAS genes that encode two proteins with collagen-like domains, Scl1 and Scl2, into B. subtilis. The fluorescent CMP labels the cells of these B. subtilis strains. Moreover, these strains bind tightly to a surface of mammalian collagen. These data are consistent with streptococcal collagen forming triple helices with damaged collagen in a wound bed and thus have implications for microbial virulence.
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spelling mit-1721.1/1325522021-09-21T03:41:18Z Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections Ellison, Aubrey J Dempwolff, Felix Kearns, Daniel B Raines, Ronald T Copyright © 2020 American Chemical Society. Group A Streptococcus (GAS) displays cell-surface proteins that resemble human collagen. We find that a fluorophore-labeled collagen mimetic peptide (CMP) labels GAS cells but not Escherichia coli or Bacillus subtilis cells, which lack such proteins. The CMP likely engages in a heterotrimeric helix with endogenous collagen, as the nonnatural d enantiomer of the CMP does not label GAS cells. To identify a molecular target, we used reverse genetics to "knock-in"the GAS genes that encode two proteins with collagen-like domains, Scl1 and Scl2, into B. subtilis. The fluorescent CMP labels the cells of these B. subtilis strains. Moreover, these strains bind tightly to a surface of mammalian collagen. These data are consistent with streptococcal collagen forming triple helices with damaged collagen in a wound bed and thus have implications for microbial virulence. 2021-09-20T18:23:00Z 2021-09-20T18:23:00Z 2020-11-16T13:57:34Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/132552 en 10.1021/ACSINFECDIS.0C00073 ACS Infectious Diseases Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) PMC
spellingShingle Ellison, Aubrey J
Dempwolff, Felix
Kearns, Daniel B
Raines, Ronald T
Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title_full Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title_fullStr Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title_full_unstemmed Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title_short Role for Cell-Surface Collagen of Streptococcus pyogenes in Infections
title_sort role for cell surface collagen of streptococcus pyogenes in infections
url https://hdl.handle.net/1721.1/132552
work_keys_str_mv AT ellisonaubreyj roleforcellsurfacecollagenofstreptococcuspyogenesininfections
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AT kearnsdanielb roleforcellsurfacecollagenofstreptococcuspyogenesininfections
AT rainesronaldt roleforcellsurfacecollagenofstreptococcuspyogenesininfections