Searching for new agents against Enterobacteriaceae from nature: approaches, potential plant species, isolated compounds, and their respective properties

The rising trend of antibiotic-resistant infections around the world and the low antimicrobials development pipeline volume are necessitating continued efforts in the search for novel treatment options. The prominent success from fungi and bacteria as sources of antibiotics has long motivated widespread efforts in the search for antibacterial compounds from other natural sources including plants. This review aimed at appraising the approaches and outcomes from studies commissioned to evaluate the antibacterial activities of crude plant extracts and phytochemicals. Notably, the existing traditional practices provided the greatest motivation in screening for antibacterial properties of plants, whereby the need to validate ethnomedically reported potentials formed a crucial objective. Moreover, choices of experimental techniques to address different objectives were largely dependent on the prevailing access to resources, facilities, and technical skills. The lack of streamlined guidelines dedicated to testing of crude plant extracts have resulted into broad methodological variations and lack of a standardized classification system for antibacterial activities exhibited by plant extracts. Furthermore, libraries of 128 extracts from different plant species and 122 phytochemicals substantially active against the Escherichia coli and Klebsiella pneumoniae were assembled. This enabled the elucidation of existing patterns between the Minimum Inhibitory Concentrations (MICs) and studied plant families, plant tissues, extractants, phytochemical classes, as well as the rules of drug-likeness, penetration and accumulation. The insights provided in this review will potentially impart the ongoing efforts with improved experimental designs, inspire ideas for further studies and contribute to successful hunting for new antibacterial chemical scaffolds via in silico approaches. Graphical abstract