Abstract
The growing threat of antibiotic resistance in bacteria is a critical public health concern. Combining natural compounds with antimicrobial agents is an alternative approach to improve the antibacterial efficacy and safety of these agents. The strategy is to restore the effectiveness of existing antibiotics while minimizing the required concentrations of antibiotics or antimicrobial agents. This study aimed to isolate the endophytic fungi from medicinal plants, including Lantana camara, Orthosiphon aristatus, Mansonia gagei, Terminalia bellirica, Oroxylum indicum, Elaeagnus latifolia, Talinum paniculatum, and Capsicum annuum, and evaluate the combined antibacterial efficacy with selected antibiotics or ethylenediaminetetraacetic acid (EDTA) against Pseudomonas aeruginosa. The antimicrobial activity of the extracts was assessed using agar well diffusion and broth microdilution methods. The minimum inhibitory concentration (MIC) values of the extracts were 32-64 µg/mL against Escherichia coli, and 512-2,048 µg/mL against P. aeruginosa, respectively. Time-kill assays demonstrated the bacteriostatic effect of the extracts. The checkerboard microbroth dilution method was performed to determine the synergistic effect between endophytic fungal extracts and antibiotics or EDTA. The synergistic effect was observed in the extractions of endophytic fungi isolated from M. gagei, T. bellirica, O. indicum, E. latifolia, T. paniculatum, and C. annuum combined with EDTA against P. aeruginosa. Combinations of endophytic fungi with EDTA, which exhibited a synergistic effect, demonstrated bactericidal action against Gram-negative bacteria. The present study suggests that combining endophytic fungal extracts and EDTA could be an essential strategy for combating pathogenic Gram-negative bacteria.