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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Main Authors: Dan Mu, Yongxin Luan, Lin Wang, Zeyuan Gao, Panpan Yang, Shisong Jing, Yanling Wang, Hua Xiang, Tiedong Wang, Dacheng Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
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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