Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo
Suilysin (SLY) plays a critical role in Streptococcus suis infections making it an ideal target to the combat infection caused by this pathogen. In the present study, we found that piceatannol (PN), a natural compound, inhibits pore-formation by blocking the oligomerization of SLY without affecting...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2020.593588/full |
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| author | Guizhen Wang Guizhen Wang Guizhen Wang Yawen Gao Yawen Gao Xiuhua Wu Xiue Gao Min Zhang Hongmei Liu Tianqi Fang Tianqi Fang |
| author_facet | Guizhen Wang Guizhen Wang Guizhen Wang Yawen Gao Yawen Gao Xiuhua Wu Xiue Gao Min Zhang Hongmei Liu Tianqi Fang Tianqi Fang |
| author_sort | Guizhen Wang |
| collection | DOAJ |
| description | Suilysin (SLY) plays a critical role in Streptococcus suis infections making it an ideal target to the combat infection caused by this pathogen. In the present study, we found that piceatannol (PN), a natural compound, inhibits pore-formation by blocking the oligomerization of SLY without affecting the growth of S. suis and the expression of SLY. Furthermore, PN alleviated the J774 cell damage and the expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1β) induced by S. suis in vitro. The computational biology and biochemistry results indicated that PN binds to the joint region of D2 and D4 in SLY, and Asn57, Pro58, Pro59, Glu76, Ile379, Glu380, and Glu418 were critical residues involved in the binding. The binding effect between PN and SLY hindered the SLY monomers from forming the oligomers, thereby weakening the hemolytic activity of SLY. This mechanism was also verified by hemolysis analysis and analysis of KA formation after site-specific mutagenesis. Furthermore, PN protected mice from S. suis infections by reducing bacterial colony formation and the inflammatory response in target organs in vivo. These results indicate that PN is a feasible drug candidate to combat S. suis infections. |
| first_indexed | 2024-12-17T01:12:52Z |
| format | Article |
| id | doaj.art-5e8695b6c0644f4c9a6d3c7c76aebc29 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-17T01:12:52Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5e8695b6c0644f4c9a6d3c7c76aebc292022-12-21T22:09:06ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-11-011110.3389/fmicb.2020.593588593588Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivoGuizhen Wang0Guizhen Wang1Guizhen Wang2Yawen Gao3Yawen Gao4Xiuhua Wu5Xiue Gao6Min Zhang7Hongmei Liu8Tianqi Fang9Tianqi Fang10Department of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, ChinaCollege of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaCollege of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaCollege of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaDepartment of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaSuilysin (SLY) plays a critical role in Streptococcus suis infections making it an ideal target to the combat infection caused by this pathogen. In the present study, we found that piceatannol (PN), a natural compound, inhibits pore-formation by blocking the oligomerization of SLY without affecting the growth of S. suis and the expression of SLY. Furthermore, PN alleviated the J774 cell damage and the expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1β) induced by S. suis in vitro. The computational biology and biochemistry results indicated that PN binds to the joint region of D2 and D4 in SLY, and Asn57, Pro58, Pro59, Glu76, Ile379, Glu380, and Glu418 were critical residues involved in the binding. The binding effect between PN and SLY hindered the SLY monomers from forming the oligomers, thereby weakening the hemolytic activity of SLY. This mechanism was also verified by hemolysis analysis and analysis of KA formation after site-specific mutagenesis. Furthermore, PN protected mice from S. suis infections by reducing bacterial colony formation and the inflammatory response in target organs in vivo. These results indicate that PN is a feasible drug candidate to combat S. suis infections.https://www.frontiersin.org/articles/10.3389/fmicb.2020.593588/fullStreptococcus suispiceatannolsuilysinvirulencemolecular modeling |
| spellingShingle | Guizhen Wang Guizhen Wang Guizhen Wang Yawen Gao Yawen Gao Xiuhua Wu Xiue Gao Min Zhang Hongmei Liu Tianqi Fang Tianqi Fang Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo Frontiers in Microbiology Streptococcus suis piceatannol suilysin virulence molecular modeling |
| title | Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo |
| title_full | Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo |
| title_fullStr | Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo |
| title_full_unstemmed | Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo |
| title_short | Inhibitory Effect of Piceatannol on Streptococcus suis Infection Both in vitro and in vivo |
| title_sort | inhibitory effect of piceatannol on streptococcus suis infection both in vitro and in vivo |
| topic | Streptococcus suis piceatannol suilysin virulence molecular modeling |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2020.593588/full |
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