Table 1.
Examples of applications of metabolomics to determine the mode of action of drugs and other compounds with antimicrobial activity
| Organism | Test compound | Metabolomics approach | Target identified | Reference |
|---|---|---|---|---|
| T. brucei | Eflornithine | Untargeted LC-MS (HILIC-Orbitrap) | Ornithine decarboxylase | (Vincent et al. 2012) |
| T. brucei | Nifurtimox | Untargeted LC-MS (HILIC-Orbitrap) | Complex: involves nucleotides, oxidative stress and an active metabolite | (Vincent et al. 2012) |
| T. brucei | 5-fluoro-2′-deoxyuridine | Untargeted LC-MS (HILIC-Orbitrap) | Thymidylate synthase inhibited by active metabolite | (Ali et al. 2013) |
| T. brucei | 5-fluoroorotate and 5-fluorouracil | Untargeted LC-MS (HILIC-Orbitrap) | RNA modification (fluorinated uracil residues) | (Ali et al. 2013) |
| L. infantum | Antimony (III) | Untargeted CE-MS (CE-TOF) | Oxidative stress (sulphur amino acids and polyamines) | (Canuto et al. 2012) |
| P. falciparum | Atovaquone and CK-2-68 | Targeted LC-MS (HILIC-QQQ) | Dihydroorotate dehydrogenase (via mitochondrial electron transport chain) | (Biagini et al. 2012) |
| P. falciparum | Fosmidomycin | Targeted LC-MS (ion paired reversed-phase – QQQ) | Methylerythritol phosphate cytidyltransferase (IspD) and deoxyxylulose phosphate reductoisomerase (DXR) | (Zhang et al. 2011) |
| P. falciparum | Eflornithine with MDL73811 | Targeted LC-MS (HILIC-QQQ) | Polyamine synthesis | (van Brummelen et al. 2009) |
| Staphylococcus aureus | Triphenylbismuth dichloride | Targeted 1H NMR | Pyruvate dehydrogenase | (Birkenstock et al. 2012) |
| S. aureus | Guanidinomethylbenzoates and guanidinobenzamides | Untargeted GC-MS | Classified as having similar mechanism to clindamycin | (Liu et al. 2009) |
| Escherichia coli | Trimethoprim | Targeted LC-MS (HILIC-QQQ) | Dihydrofolate reducatase and folylpoly-γ-glutamate synthetase | (Kwon et al. 2008) |
| E. coli Pseudomonas aeruginosa | 11 common antibiotics | Targeted CE-UV | Classification of mechanisms by correlation analysis | (Gao et al. 2007) |
| Mycobacterium smegmatis | 12 drugs and 3 chemical leads | Untargeted 1H NMR | Classification of mechanisms by multivariate analysis | (Halouska et al. 2012) |
| M. smegmatis | D-cycloserine | Untargeted 1H NMR | D-alanine-D-alanine ligase | (Halouska et al. 2007) |