The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus
ABSTRACTStaphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of pneumonia, resulting in severe morbidity and mortality in adults and children. Sortase A (SrtA), which mediates the anchoring of cell surface proteins in the cell wall, is an...
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Taylor & Francis Group
2020-01-01
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Series: | Emerging Microbes and Infections |
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Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1711817 |
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author | Dan Mu Yongxin Luan Lin Wang Zeyuan Gao Panpan Yang Shisong Jing Yanling Wang Hua Xiang Tiedong Wang Dacheng Wang |
author_facet | Dan Mu Yongxin Luan Lin Wang Zeyuan Gao Panpan Yang Shisong Jing Yanling Wang Hua Xiang Tiedong Wang Dacheng Wang |
author_sort | Dan Mu |
collection | DOAJ |
description | ABSTRACTStaphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of pneumonia, resulting in severe morbidity and mortality in adults and children. Sortase A (SrtA), which mediates the anchoring of cell surface proteins in the cell wall, is an important virulence factor of S. aureus. Here, we found that salvianolic acid A (Sal A), which is a natural product that does not affect the growth of S. aureus, could inhibit SrtA activity (IC50 = 5.75 μg/ml) and repress the adhesion of bacteria to fibrinogen, the anchoring of protein A to cell wall, the biofilm formation, and the ability of S. aureus to invade A549 cells. Furthermore, in vivo studies demonstrated that Sal A treatment reduced inflammation and protected mice against lethal pneumonia caused by MRSA. More significantly, full protection (a survival rate of 100%) was achieved when Sal A was administered in combination with latamoxef. Together, these results indicate that Sal A could be developed into a promising therapeutic drug to combat MRSA infections while limiting resistance development. |
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spelling | doaj.art-9ddf92c1a9bf418f8be0ebe764472db72024-03-11T16:04:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019116917910.1080/22221751.2020.1711817The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureusDan Mu0Yongxin Luan1Lin Wang2Zeyuan Gao3Panpan Yang4Shisong Jing5Yanling Wang6Hua Xiang7Tiedong Wang8Dacheng Wang9College of Animal Science, Jilin University, Changchun, People’s Republic of ChinaDepartment of Neurosurgery, First Hospital of Jilin University, Jilin University, Changchun, People’s Republic of ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of ChinaCollege of Animal Science, Jilin University, Changchun, People’s Republic of ChinaDepartment of Pharmacology, College of Basic Medical Science, Jilin University, Changchun, People’s Republic of ChinaCollege of Animal Science, Jilin University, Changchun, People’s Republic of ChinaCollege of Animal Science, Jilin University, Changchun, People’s Republic of ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun, People’s Republic of ChinaCollege of Animal Science, Jilin University, Changchun, People’s Republic of ChinaCollege of Animal Science, Jilin University, Changchun, People’s Republic of ChinaABSTRACTStaphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of pneumonia, resulting in severe morbidity and mortality in adults and children. Sortase A (SrtA), which mediates the anchoring of cell surface proteins in the cell wall, is an important virulence factor of S. aureus. Here, we found that salvianolic acid A (Sal A), which is a natural product that does not affect the growth of S. aureus, could inhibit SrtA activity (IC50 = 5.75 μg/ml) and repress the adhesion of bacteria to fibrinogen, the anchoring of protein A to cell wall, the biofilm formation, and the ability of S. aureus to invade A549 cells. Furthermore, in vivo studies demonstrated that Sal A treatment reduced inflammation and protected mice against lethal pneumonia caused by MRSA. More significantly, full protection (a survival rate of 100%) was achieved when Sal A was administered in combination with latamoxef. Together, these results indicate that Sal A could be developed into a promising therapeutic drug to combat MRSA infections while limiting resistance development.https://www.tandfonline.com/doi/10.1080/22221751.2020.1711817Staphylococcus aureussortase Asalvianolic acid Apneumoniainhibitor |
spellingShingle | Dan Mu Yongxin Luan Lin Wang Zeyuan Gao Panpan Yang Shisong Jing Yanling Wang Hua Xiang Tiedong Wang Dacheng Wang The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus Emerging Microbes and Infections Staphylococcus aureus sortase A salvianolic acid A pneumonia inhibitor |
title | The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus |
title_full | The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus |
title_fullStr | The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus |
title_full_unstemmed | The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus |
title_short | The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus |
title_sort | combination of salvianolic acid a with latamoxef completely protects mice against lethal pneumonia caused by methicillin resistant staphylococcus aureus |
topic | Staphylococcus aureus sortase A salvianolic acid A pneumonia inhibitor |
url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1711817 |
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