Abstract
Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S. aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values against S. aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S. aureus, and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.