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

Abstract

<i>Staphylococcus aureus</i> (<i>S. aureus</i>), especially methicillin-resistant <i>Staphylococcus aureus</i> (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 <i>S. aureus</i>. Here, we found that salvianolic acid A (Sal A), which is a natural product that does not affect the growth of <i>S. aureus</i>, 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 <i>S. aureus</i> to invade A549 cells. Furthermore, <i>in vivo</i> 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.