The Computational and Experimental Study of M1 and M2 Peptides Combined with Vancomycin to Control Vancomycin-Intermediate Enterococcus faecalis.

Melittin (MLT), an antimicrobial peptide, is considered due to its wide range of antimicrobial properties against Gram-negative and Gram-positive bacteria. In this study, we performed in silico and in vitro studies for the evaluation of the synergistic effect of M1 and M2 peptides derived from MLT to limit vancomycin intermediate E. faecalis. Results obtained from coarse-grained simulations indicated significant destruction during the penetration of the M1 and M2 peptides into the E. faecalis membrane model. The trajectory results also revealed notable movements of 2.381 nm and 2.758 nm within the membrane for M1 and M2 peptides, respectively. The synergistic effect of MLT, M1, and M2 peptides with vancomycin was evaluated to inhibit the growth of a VIE clinical isolate using the established checkerboard method. MTT assays and hemolysis tests were conducted to examine the toxicity of the peptides. The combination therapy of vancomycin with the peptides led to an 80-fold reduction in the MIC value of vancomycin (from 8 to 0.125 µg/ml). In contrast, it led to a 13.33-fold reduction in the MIC value of MLT, an eightfold decrease in the MIC value of both M1 and M2 peptides. Based on FICI values, a synergistic effect was observed between MLT, M1, and M2 with vancomycin. MTT assay and hemolysis results indicated a notable reduction in the toxicity of the peptides at the synergistic concentrations. In conclusion, the combination therapy of MLT and M1 and M2 peptides with the vancomycin antibiotic could be an appealing therapeutic strategy against E. faecalis infections.