The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus

Autor: Dan Mu, Yongxin Luan, Lin Wang, Zeyuan Gao, Panpan Yang, Shisong Jing, Yanling Wang, Hua Xiang, Tiedong Wang, Dacheng Wang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 9, Iss 1, Pp 169-179 (2020)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2020.1711817
Popis: 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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