Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Objective To investigate the mechanism of antibacterial activity of luteolin (LUT) against methicillin-resistant Staphylococcus aureus (MRSA). Methods The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent, ATPase inhibitors, and peptidoglycan (PGN) derived from Staphylococcus aureus ( S. aureus ). Also, transmission electron microscopy was used to monitor survival characteristics and changes in S. aureus morphology. Results Compared to the LUT alone, the optical density of suspensions treated with the combination of 125 μg/mL Tris and 250 μg/mL N , N′ -dicyclohexylcarbodiimide were reduced to 60% and 46% of the control, respectively. PGN (15.6 μg/mL) gradually impeded the activity of LUT, and PGN (62.5 μg/mL) completely blocked the activity of LUT on S. aureus . Conclusions Increased susceptibility to LUT with the Tris-dicyclohexylcarbodiimide combinations is evident in all tested MRSA isolates. The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase. S. aureus PGN directly blocks the antibacterial activity of LUT, suggesting the direct binding of LUT with PGN. These findings may be validated for the development of antibacterial agent for low MRSA resistance.