Microbial resistance to antibiotics is an escalating problem world-wide with an enormous impact on human health that have led to an urgent need for new antibiotics. The situation is exacerbated by bacteria resistant to multiple antibiotic classes, which causes infections that are very difficult to treat. In particular, the ‘ESKAPE’ pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aureginosa and Enterobacter spp.) have become notoriously problematic by gaining multi-drug resistance and becoming more virulent. The emergence of multi-drug resistant bacteria have led to a renewed interest in drug discovery from natural sources including plants.
Medicinal plants have been used for thousands of years for their antiseptic qualities. The plants produce a vast array of structurally diverse secondary metabolites, many of which have been shown to have antimicrobial activity. However, plants are still a largely untapped biological resource. It has been estimated that only 15% of higher plant species have been phyto-chemically analysed, and even a smaller percentage evaluated for their antibacterial properties.
The major aim of this study is to identify and characterise novel compounds in Australian Myrtaceae species (Eucalyptus, Corymbia and Angophora) that have antimicrobial activity against multiple ESKAPE pathogens.
Three distinct bioactivity assays will be used to assess antimicrobial activity in extracts from these species. Firstly, standard high-throughput MIC/MBC assays will be used to evaluate bactericidal and bacteriostatic activity. Secondly, biofilm specific screens will be used to determine if extracts inhibit biofilm formation of selected species. Thirdly, we will use a reporter-gene assay to identify inhibitors of the RegA response regulator of Citrobacter rodentium. Response regulators are interesting antimicrobial targets because the inhibition of key virulence regulators may attenuate the pathogenicity of the target bacteria while leaving the commensal microflora intact. Selected fractions with bioactivity will be further purified, and pure compounds subjected to additional functional assays.