Metabolomics: towards acceleration of antibacterial plant-based leads discovery

Abstract

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.

Inhibition of Cronobacter sakazakii in an infant simulator of the human intestinal microbial ecosystem using a potential synbiotic

“…Metabolomics analyses gave some insight into the possible factors that could inhibit C. sakazakii. Untargeted metabolomics and PCA have been used to screen for potential bioactive molecules from plants and evaluate the metabolic changes of foodborne pathogens post-exposure to biochemical or physical treatments (Maifiah et al, 2017;Tian et al, 2018;Sieniawska and Georgiev, 2022). In this study, the PCA biplot revealed differences in metabolite profile within the SHIME compartments that may be generally associated with C. sakazakii levels.…”

Molecular insight into thymoquinone mechanism of action against Mycobacterium tuberculosis

“…Natural products are promising antimicrobials that can influence bacterial cells on different metabolic and functional levels ( Sieniawska and Georgiev, 2022 ). They usually have multiple cellular targets other than synthetic antibiotics.…”

“…The influence of TQ on bacterial cells can be monitored by metabolomics, which detects a large number of analytes and reflects the complexity of metabolic alterations. The significantly changed metabolites indicate targeted metabolic pathways and thus reflect the direct or indirect influence of the test compound on bacteria ( Sieniawska and Georgiev, 2022 ). To get insight into the regulation of bacteria’s response to stress factors, a more comprehensive gene-metabolite approach is required ( Sieniawska and Georgiev, 2022 ).…”

“…The significantly changed metabolites indicate targeted metabolic pathways and thus reflect the direct or indirect influence of the test compound on bacteria ( Sieniawska and Georgiev, 2022 ). To get insight into the regulation of bacteria’s response to stress factors, a more comprehensive gene-metabolite approach is required ( Sieniawska and Georgiev, 2022 ). Therefore, in this study, we applied both untargeted metabolomics and sigma factor gene expression analysis to determine the TQ mechanism of action in mycobacterial cells.…”