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Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity
Streptococcus suis, a Gram-positive pathogen, is widely recognized as an important agent of swine infection, and it is also known to cause a variety of zoonoses, such as meningitis, polyarthritis and pneumonia. Suilysin (SLY), an extracellular pore-forming toxin that belongs to the cholesterol-depen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357624/ https://www.ncbi.nlm.nih.gov/pubmed/28373868 http://dx.doi.org/10.3389/fmicb.2017.00460 |
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author | Li, Gen Lu, Gejin Qi, Zhimin Li, Hongen Wang, Lin Wang, Yanhui Liu, Bowen Niu, Xiaodi Deng, Xuming Wang, Jianfeng |
author_facet | Li, Gen Lu, Gejin Qi, Zhimin Li, Hongen Wang, Lin Wang, Yanhui Liu, Bowen Niu, Xiaodi Deng, Xuming Wang, Jianfeng |
author_sort | Li, Gen |
collection | PubMed |
description | Streptococcus suis, a Gram-positive pathogen, is widely recognized as an important agent of swine infection, and it is also known to cause a variety of zoonoses, such as meningitis, polyarthritis and pneumonia. Suilysin (SLY), an extracellular pore-forming toxin that belongs to the cholesterol-dependent cytolysin family, is an essential virulence factor of S. suis capsular type 2 (SS2). Here, we found that morin hydrate (morin), a natural flavonoid that lacks anti-SS2 activity, inhibits the hemolytic activity of SLY, protects J774 cells from SS2-induced injury and protects mice from SS2 infection. Further, by molecular modeling and mutational analysis, we found that morin binds to the “stem” domain 2 in SLY and hinders its transformation from the monomer form to the oligomer form, which causes the loss of SLY activity. Our study demonstrates that morin hinders the cell lysis activity of SLY through a novel mechanism of interrupting the heptamer formation. These findings may lead to the development of promising therapeutic candidates for the treatment of SS2 infections. |
format | Online Article Text |
id | pubmed-5357624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53576242017-04-03 Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity Li, Gen Lu, Gejin Qi, Zhimin Li, Hongen Wang, Lin Wang, Yanhui Liu, Bowen Niu, Xiaodi Deng, Xuming Wang, Jianfeng Front Microbiol Microbiology Streptococcus suis, a Gram-positive pathogen, is widely recognized as an important agent of swine infection, and it is also known to cause a variety of zoonoses, such as meningitis, polyarthritis and pneumonia. Suilysin (SLY), an extracellular pore-forming toxin that belongs to the cholesterol-dependent cytolysin family, is an essential virulence factor of S. suis capsular type 2 (SS2). Here, we found that morin hydrate (morin), a natural flavonoid that lacks anti-SS2 activity, inhibits the hemolytic activity of SLY, protects J774 cells from SS2-induced injury and protects mice from SS2 infection. Further, by molecular modeling and mutational analysis, we found that morin binds to the “stem” domain 2 in SLY and hinders its transformation from the monomer form to the oligomer form, which causes the loss of SLY activity. Our study demonstrates that morin hinders the cell lysis activity of SLY through a novel mechanism of interrupting the heptamer formation. These findings may lead to the development of promising therapeutic candidates for the treatment of SS2 infections. Frontiers Media S.A. 2017-03-20 /pmc/articles/PMC5357624/ /pubmed/28373868 http://dx.doi.org/10.3389/fmicb.2017.00460 Text en Copyright © 2017 Li, Lu, Qi, Li, Wang, Wang, Liu, Niu, Deng and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Li, Gen Lu, Gejin Qi, Zhimin Li, Hongen Wang, Lin Wang, Yanhui Liu, Bowen Niu, Xiaodi Deng, Xuming Wang, Jianfeng Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title | Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title_full | Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title_fullStr | Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title_full_unstemmed | Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title_short | Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity |
title_sort | morin attenuates streptococcus suis pathogenicity in mice by neutralizing suilysin activity |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357624/ https://www.ncbi.nlm.nih.gov/pubmed/28373868 http://dx.doi.org/10.3389/fmicb.2017.00460 |
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