Inhibition of Growth and Biofilm Formation in Staphylococcus aureus by LLY-507

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a prevalent antibiotic-resistant pathogen underscores the urgent need for novel antibacterial agents. This study investigates the potential of LLY-507 against Gram-positive bacteria, particularly S. aureus, focusing on its antibacterial and antibiofilm properties. Here, our data exhibited the favorable antibacterial activity of LLY-507 with MIC₅₀ and MIC₉₀ values of 25 μM against S. aureus. Additionally, LLY-507 at sub-MIC concentrations effectively reduced the planktonic growth and biofilm formation of S. aureus. Proteomic analysis of S. aureus treated with LLY-507 revealed the classification of the functional proteins with significant expression level alterations in bacterial metabolism, particularly amino acid biosynthesis. Furthermore, we demonstrated the disruption of S. aureus cell integrity by LLY-507 through scanning electron microscopy (SEM) assay, membrane permeability assays, and direct binding experiments between LLY-507 and cardiolipin. Lastly, the effectiveness of LLY-507 was proven in vivo using the Galleria mellonella infection model. Overall, these findings highlight the promising antibacterial and antibiofilm activities of LLY-507 against S. aureus and provide insights into its mechanism of action, implicating its potential as a lead compound for developing novel antibacterial agents targeting Gram-positive bacteria.