Metabolomics: towards acceleration of antibacterial plant-based leads discovery

The wide and not yet fully uncovered potential of plant secondary metabolites make plants a rich source of drug leads. Metabolomics enables the study of the metabolic perturbations taking place in bacterial cells under the influence of plant-based bioactive molecules. It reveals the changes in metabolic pathways within bacteria, reflecting the reprogramming of the biochemical networks. From this point of view, metabolomics is valuable in understanding the alteration of cell functions when bacteria are subjected to metabolic stress caused by treatment with secondary metabolites, that inhibit their growth. In this review the application of metabolomics in revealing bacteria response to plant-derived secondary metabolites is presented. Metabolomics may be a way to select antibacterial plant-based bioactive secondary metabolites and to understand their mode of action. Therefore, herein the usefulness of metabolomic approach in screening for antimicrobials from plants, as well as in exploring the target points in bacteria metabolism and in uncovering the mechanisms of bacteria adaptation and resistance to natural antimicrobials are discussed. Basic chemometrics and molecular networking are successfully applied for the identification of antimicrobial molecules in complex plant mixtures. Determination of antibacterial modes of action is done through classification strategy, pathway analysis and integration of transcriptomics, genomics and metabolomics, whereas, comparative metabolomics and integrative approach is useful in revealing the bacterial mechanisms of resistance.