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Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1)
Expression of bacteriophage lysin(SM1) by Streptococcus oralis strain SF100 is thought to be important for the pathogenesis of infective endocarditis, due to its ability to mediate bacterial binding to fibrinogen. To better define the lysin(SM1) binding site on fibrinogen Aα, and to investigate the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263008/ https://www.ncbi.nlm.nih.gov/pubmed/34154404 http://dx.doi.org/10.1128/mBio.00746-21 |
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author | Ji, Hyun Jung Zhi, Yong Lee, Ji Hee Ahn, Ki Bum Seo, Ho Seong Sullam, Paul M. |
author_facet | Ji, Hyun Jung Zhi, Yong Lee, Ji Hee Ahn, Ki Bum Seo, Ho Seong Sullam, Paul M. |
author_sort | Ji, Hyun Jung |
collection | PubMed |
description | Expression of bacteriophage lysin(SM1) by Streptococcus oralis strain SF100 is thought to be important for the pathogenesis of infective endocarditis, due to its ability to mediate bacterial binding to fibrinogen. To better define the lysin(SM1) binding site on fibrinogen Aα, and to investigate the impact of binding on fibrinolysis, we examined the interaction of lysin(SM1) with a series of recombinant fibrinogen Aα variants. These studies revealed that lysin(SM1) binds the C-terminal region of fibrinogen Aα spanned by amino acid residues 534 to 610, with an affinity of equilibrium dissociation constant (K(D)) of 3.23 × 10(−5) M. This binding site overlaps the known binding site for plasminogen, an inactive precursor of plasmin, which is a key protease responsible for degrading fibrin polymers. When tested in vitro, lysin(SM1) competitively inhibited plasminogen binding to the αC region of fibrinogen Aα. It also inhibited plasminogen-mediated fibrinolysis, as measured by thromboelastography (TEG). These results indicate that lysin(SM1) is a bi-functional virulence factor for streptococci, serving as both an adhesin and a plasminogen inhibitor. Thus, lysin(SM1) may facilitate the attachment of bacteria to fibrinogen on the surface of damaged cardiac valves and may also inhibit plasminogen-mediated lysis of infected thrombi (vegetations) on valve surfaces. |
format | Online Article Text |
id | pubmed-8263008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-82630082021-07-23 Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) Ji, Hyun Jung Zhi, Yong Lee, Ji Hee Ahn, Ki Bum Seo, Ho Seong Sullam, Paul M. mBio Research Article Expression of bacteriophage lysin(SM1) by Streptococcus oralis strain SF100 is thought to be important for the pathogenesis of infective endocarditis, due to its ability to mediate bacterial binding to fibrinogen. To better define the lysin(SM1) binding site on fibrinogen Aα, and to investigate the impact of binding on fibrinolysis, we examined the interaction of lysin(SM1) with a series of recombinant fibrinogen Aα variants. These studies revealed that lysin(SM1) binds the C-terminal region of fibrinogen Aα spanned by amino acid residues 534 to 610, with an affinity of equilibrium dissociation constant (K(D)) of 3.23 × 10(−5) M. This binding site overlaps the known binding site for plasminogen, an inactive precursor of plasmin, which is a key protease responsible for degrading fibrin polymers. When tested in vitro, lysin(SM1) competitively inhibited plasminogen binding to the αC region of fibrinogen Aα. It also inhibited plasminogen-mediated fibrinolysis, as measured by thromboelastography (TEG). These results indicate that lysin(SM1) is a bi-functional virulence factor for streptococci, serving as both an adhesin and a plasminogen inhibitor. Thus, lysin(SM1) may facilitate the attachment of bacteria to fibrinogen on the surface of damaged cardiac valves and may also inhibit plasminogen-mediated lysis of infected thrombi (vegetations) on valve surfaces. American Society for Microbiology 2021-06-22 /pmc/articles/PMC8263008/ /pubmed/34154404 http://dx.doi.org/10.1128/mBio.00746-21 Text en Copyright © 2021 Ji et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Ji, Hyun Jung Zhi, Yong Lee, Ji Hee Ahn, Ki Bum Seo, Ho Seong Sullam, Paul M. Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title | Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title_full | Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title_fullStr | Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title_full_unstemmed | Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title_short | Inhibition of Fibrinolysis by Streptococcal Phage Lysin(SM1) |
title_sort | inhibition of fibrinolysis by streptococcal phage lysin(sm1) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263008/ https://www.ncbi.nlm.nih.gov/pubmed/34154404 http://dx.doi.org/10.1128/mBio.00746-21 |
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