The interactive antimicrobial activity of Terminalia sericea Burch ex DC. leaf extracts and conventional antibiotics against bacterial triggers of selected autoimmune inflammatory diseases

Abstract

Recent increases in antibiotic resistance and corresponding decreases in the development of new antimicrobial therapies have made new antibiotic discovery a high priority. Traditional medicines have potential for antibiotic discovery, although synergistic combinations consisting of plant extracts and conventional antibiotics may be a more effective approach. The combinations may overcome resistance and repurpose antibiotics that would otherwise be ineffective against resistant bacterial strains. In this study, Terminalia sericea leaves were extracted with solvents of varying polarity and the resultant extracts were investigated for the ability to inhibit bacterial growth using disc diffusion and liquid dilution MIC techniques. The effects of combinations of the extracts and conventional antibiotics (chloramphenicol, ciprofloxacin, erythromycin, gentamycin, penicillin-G or tetracyclin) were also tested using the checkerboard method. Combinations that exhibited synergistic interactions were further examined using isobologram analysis to determine the ideal ratios of extract-antibiotic. Toxicity was evaluated using Artemia nauplii and human dermal fibroblast (HDF) toxicity assays. The methanolic and water T. sericea extracts were good inhibitors of the microbial triggers of several autoimmune diseases, with MIC values substantially <1000 µg/mL against all bacteria tested except P. aeurginosa . The extracts were particularly potent inhibitors of Proteus spp., with MICs as low as 180 µg/mL. However, combinations of T. sericea extracts and conventional antibiotics were substantially more effective in inhibiting the growth of some bacterial species. In total, four combinations were synergistic and a further eight combinations had additive effects. Although the mechanisms of potentiation are still unclear, compounds within T. sericea extracts may mimic the actions of resistance modifying agents, thus potentiating the activity of several antibiotics that are relatively ineffective alone. Isolation of these agents may be beneficial for drug design against the bacterial triggers of rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis and rheumatic fever. All extracts, antibiotics and combinations were nontoxic in the Artemia nauplii and HDF toxicity assays, further indicating their potential for medicinal use. • Polar T. sericea extracts were strong inhibitors of bacterial growth when tested alone. • Some plant extract-antibiotic combinations were substantially more effective antibacterial agents. • Some weak antibiotics were substatially potentiated in combination with the extracts. • T. sericea extracts were nontoxic in A. nauplii and HDF assays.