Selected Australian Terminalia Species Extracts Inhibit β-Lactam Drug-Resistant Bacteria Growth and Potentiate the Activity of Conventional Antibiotics: Bioactivities and Phytochemistry

Abstract

Terminalia ferdinandiana Exell, Terminalia grandiflora Benth., Terminalia microcarpa Decne., and Terminalia muelleri Benth. (family: Combretaceae) belong to the genus Terminalia. Plants of this genus have been extensively used as traditional medicines to treat a variety of illnesses, including pathogen infections. However, we were unable to find any studies that have investigated the antibacterial activity of T. microcarpa. Similarly, whilst some preliminary studies have examined the antimicrobial properties of T. muelleri and T. grandiflora, they did not test the extracts against antibiotic-resistant pathogens. This study screens the antimicrobial activity of T. grandiflora, T. microcarpa, and T. muelleri and compares it to that of T. ferdinandiana extracts prepared from both the fruit and leaves against a range of pathogens, including multi-antibiotic-resistant strains. Solvents with varying polarities were used to extract different phytochemical constituents from the leaves of T. grandiflora, T. microcarpa, and T. muelleri and from the fruit and leaves of T. ferdinandiana. The aqueous and methanolic extracts each displayed significant antimicrobial activity when tested against the bacterial pathogens, including against the multidrug-resistant strains. When these extracts were tested in combination with selected antibiotics, some extracts potentiated the antimicrobial activity. This study identifies twelve synergistic, fifty-eight additive, and sixty non-interactive combinations, as well as thirty antagonistic effects. The extracts were evaluated for toxicity using the Artemia franciscana nauplii lethality assay (ALA) and were each classified as non-toxic, with the exception of the methanolic and aqueous T. ferdinandiana fruit extracts and the aqueous and ethyl acetate T. ferdinandiana leaf extracts. Metabolomic analysis using liquid chromatography–mass spectrometry (LC-MS) highlighted several flavonoids and tannins that may contribute to the antimicrobial activities reported herein. The potential antibacterial mechanism(s) of the T. ferdinandiana extracts are discussed in this study.