Synergistic action of endophytic fungi secondary metabolites against multidrug-resistant strains of Staphylococcus aureus

The global threat to treatment of infections associated with multidrug-resistant microorganisms as well as side effects associated with combination therapy calls for the urgent development of new medicines to address these challenges. Endophytic fungi are efficient bio synthesizers and offer a wide array of these reliable bioactive compounds. The present study is aimed at evaluating the effect of combined extracts of endophytic fungi isolated from the leaves of Musa paradisiaca against multidrug-resistant Staphylococcus aureus (MRSA) strains. Screening for multidrug resistance was carried out using the Kirby-Bauer disc diffusion assay followed by a preliminary assay of endophytic fungal extracts bioactivity using agar diffusion assay against selected MRSA. A synergistic study using checkerboard assay technique was performed, then extracts were subjected to quantitative evaluation of secondary metabolites using Gas Chromatography with Flame Ionization Detector. Axenic cultures of five endophytic fungi from M. paradisiaca (EMp1-Emp5) were isolated from the sampled leaves. All the endophytic fungal extracts inhibited the growth of all the multi-drug resistant Staphylococcus aureus at 0.5 mg/mL. Varying inhibition zones that were concentration-dependent were observed. The combined effects of EMp3 and EMp5 extracts at 9:1; 8:2; 4:6; 3:7; and 2:8 combination ratios produced synergistic effects against S. aureus (S18) with very low Fractional inhibitory Concentrations of 0.03:0.01, 0.01:0.01, 0.006:0.02, 0.01:0.04 and 0.01:0.1 mg/mL respectively. Several bioactive secondary metabolites such as anthocyanin, (-) epicatechin, naringenin, resveratrol, catechin, rutin, phenol were produced by the fungal endophytes. Our findings further affirm fungal endophytes associated with M. paradisiaca leaves as producers of natural antibacterial agents with synergistic potentials.