In Vitro Synergistic Inhibitory Effects of Plant Extract Combinations on Bacterial Growth of Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common pathogens of healthcare-associated infections. Medicinal plants have long been used in the traditional treatment of diseases or syndromes worldwide. Combined use of plant extracts could improve the effectiveness of pharmacological action by obtaining synergism, acting on multiple targets simultaneously, reducing the doses of individual components, and minimizing side effects. We aimed to investigate the synergistic inhibitory effects of selected medicinal plants (Caesalpinia sappan L. (CS), Glycyrrhiza uralensis Fisch. (GU), Sanguisorba officinalis L. (SO), and Uncaria gambir Roxb. (UG)) on the bacterial growth of MRSA and its clinical isolates. SO and UG extracts generated the best synergistic interaction as adjudged by checkerboard synergy assays. MICs of the individual extracts decreased 4-fold from 250 to 62.5 μg/mL, respectively. The SO + UG combination was further evaluated for its effects on bacterial growth inhibition, minimum bactericidal/inhibitory concentration (MBC/MIC) ratio, and time-kill kinetics. The results indicate that the SO + UG combination synergistically inhibited the bacterial growth of MRSA strains with bactericidal effects. SO + UG combination also exhibited more potent effects against clinical isolates. In multistep resistance selection experiments, both standard and isolates of MRSA showed no resistance to the SO + UG combination even after repeated exposure over fourteen passages. Our data suggest that using plant extract combinations could be a potential strategy to treat MRSA infections.