Synergistic Antibacterial Activity of Lupinifolin and Protein Synthesis Inhibitors Against Enterococcus faecalis and Enterococcus faecium

Antibacterial enhancers can increase the activity of currently-available antibacterial drugs, and their development is one of the feasible strategies to counteract antibacterial resistance. This study aims to investigate the effects of lupinifolin (isolated from Derris reticulata stems) in combination with antibacterial drugs acting as protein synthesis inhibitors—including streptomycin, chloramphenicol, and tetracycline—against Enterococcus faecalis and Enterococcus faecium. The Fractional Inhibitory Concentration Index (FICI) was obtained from a checkerboard assay to indicate the antibacterial activity of a lupinifolin–drug combination. The combinations of lupinifolin and streptomycin or chloramphenicol showed synergistic antibacterial activity against E. faecalis (TISTR 379 and DMST 4736) and E. faecium (TISTR 2058), with median FICIs of ≤ 0.5 (n=4–5); additionally, lupinifolin combined with streptomycin showed a potential synergism against E. faecium DMST 4743 (FICI < 0.5156, n=3). However, the combination of lupinifolin and tetracycline resulted in no interaction against any enterococcal strain examined (FICIs ≥ 1). In conclusion, lupinifolin potentially plays a role as an antibacterial intensifier against E. faecalis and E. faecium when used in combination with certain protein synthesis inhibitors, specifically streptomycin and chloramphenicol; nonetheless, more research is needed to examine the synergistic antibacterial mechanism of the combinations.