Synergistic interactions between artocarpin-rich extract, lawsone methyl ether and ampicillin on anti-MRSA and their antibiofilm formation

Artocarpin-rich extract (ARE) was prepared using a green technology and standardized to contain 49 center dot 6% w/w artocarpin, while lawsone methyl ether was prepared using a green semi-synthesis. ARE, LME and ampicillin exhibited weak anti-MRSA activity with the MICs of 31 center dot 2-62 center dot 5 mu g/ml. Based on the checkerboard assay, the synergistic interaction between ARE (0 center dot 03 mu g/ml) and LME (0 center dot 49 mu g/ml) against four MRSA isolates were observed with the fractional inhibitory concentration index (FICI) value of 0 center dot 008, while those of ARE (1 center dot 95-7 center dot 81 mu g/ml) and ampicillin (0 center dot 49 mu g/ml) as well as LME (0 center dot 49-1 center dot 95 mu g/ml) and ampicillin (0 center dot 49 mu g/ml) were 0 center dot 016-0 center dot 257. The time kill confirmed the synergistic interactions against MRSA with different degrees. The combination of ARE and LME as well as its combinations with ampicillin altered the membrane permeability of MRSA, which led to release of the intracellular materials. In addition, each compound inhibited the biofilm formation of standard MRSA (DMST 20654) and the clinical isolate (MRSA 1096). These findings suggested that cocktails containing ARE and LME might be used to overcome problems associated with MRSA. Additionally, the results implied that combination of either ARE or LME with available conventional antibiotic agents might be effective in countering these perilous pathogens.