Postulating Modes of Action of Compounds with Antimicrobial Activities through Metabolomics Analysis

Liu, Yi; Wen, Jie; Wang, Yunduo; Li, Yan; Xu, Weilin

doi:10.1365/s10337-009-1447-7

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…The untargeted nature of metabolomics has allowed rapid and unbiased classification of numerous antimicrobial compounds according to their modes of action (Gao et al 2007; Liu et al 2009; Halouska et al 2012). Investigation of the metabolic response of Staphylococcus aureus to triphenylbismuthdichloride revealed pyruvate dehydrogenase as a target for this novel antibiotic (Birkenstock et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Determination of antiprotozoal drug mechanisms by metabolomics approaches

Creek

Barrett

2013

Parasitology

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SUMMARYThe discovery, development and optimal utilization of pharmaceuticals can be greatly enhanced by knowledge of their modes of action. However, many drugs currently on the market act by unknown mechanisms. Untargeted metabolomics offers the potential to discover modes of action for drugs that perturb cellular metabolism. Development of high resolution LC-MS methods and improved data analysis software now allows rapid detection of drug-induced changes to cellular metabolism in an untargeted manner. Several studies have demonstrated the ability of untargeted metabolomics to provide unbiased target discovery for antimicrobial drugs, in particular for antiprotozoal agents. Furthermore, the utilization of targeted metabolomics techniques has enabled validation of existing hypotheses regarding antiprotozoal drug mechanisms. Metabolomics approaches are likely to assist with optimization of new drug candidates by identification of drug targets, and by allowing detailed characterization of modes of action and resistance of existing and novel antiprotozoal drugs.

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Section: Introductionmentioning

confidence: 99%

Determination of antiprotozoal drug mechanisms by metabolomics approaches

Creek

Barrett

2013

Parasitology

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“…However, because these transcriptomic screens are still relatively costly, there is a great interest in applying metabolomics analyses to predict natural product modes of action using either natural product extracts 236 or purified compounds. 237-242 Vincent et al have recently shown untargeted metabolomics can effectively identify compound modes of action when specific metabolic pathways are the primary drug target. 243 Metabolomic consequences of drug combinations may additionally be able to identify synergism, or antagonism between coadministered drug therapies.…”

Section: Investigations Of Secondary Metabolite Bioactivitymentioning

confidence: 99%

Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites

2017

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The labor-intensive process of microbial natural product discovery is contingent upon identifying discrete secondary metabolites of interest within complex biological extracts, which contain inventories of all extractable small molecules produced by an organism or consortium. Historically, compound isolation prioritization has been driven by observed biological activity and/or relative metabolite abundance and followed by dereplication via accurate mass analysis. Decades of discovery using variants of these methods has generated the natural pharmacopeia but also contributes to recent high rediscovery rates. However, genomic sequencing reveals substantial untapped potential in previously mined organisms, and can provide useful prescience of potentially new secondary metabolites that ultimately enables isolation. Recently, advances in comparative metabolomics analyses have been coupled to secondary metabolic predictions to accellerate bioactivity and abundance-independent discovery work flows. In this review we will discuss the various analytical and computational techniques that enable MS-based metabolomic applications to natural product discovery and discuss the future prospects for comparative metabolomics in natural product discovery.

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“…Thus, it was concluded that the MOA of berberine may be similar to that of rifampicin or norfloxacin. Using also S. aureus as the model organism, Liu et al (2010) performing GC/MS metabolomics in combination with multivariate pattern recognition analyses concluded that the MOA of the four synthesized antibiotics under study resemble that of clindamycin which inhibits protein synthesis by reversibly binding to the 50S subunit of ribosomes. In addition, metabolites such as D-glucose, proline, and phosphoric and propanoic acids were identified as biomarkers for the observed toxicity.…”

Section: Antifungal and Antibiotic Compoundsmentioning

confidence: 99%

Metabolomics in pesticide research and development: review and future perspectives

Aliferis

Chrysayi-Tokousbalides

2010

Metabolomics

114

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The emerge of metabolomics within functional genomics has provided a new dimension in the study of biological systems. In regards to the study of agroecosystems, metabolomics enables monitoring of metabolic changes in association with biotic or abiotic agents such as agrochemicals. Focusing on crop protection chemicals, a great effort has been given towards the development of crop protection agents safer for consumers and the environment and more efficient than the existing ones. Within this framework, metabolomics has so far been a valuable tool for high-throughput screening of bioactive substances in order to discover those with high selectivity, unique modes-of-action, and acceptable eco-toxicological/toxicological profiles. Here, applications of metabolomics in the investigation of the modes-of-action and ecotoxicological-toxicological risk assessment of bioactive compounds, mining of biological systems for the discovery of bioactive metabolites, and the risk assessment of genetic modified crops are discussed.

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Postulating Modes of Action of Compounds with Antimicrobial Activities through Metabolomics Analysis

Cited by 12 publications

References 30 publications

Determination of antiprotozoal drug mechanisms by metabolomics approaches

Determination of antiprotozoal drug mechanisms by metabolomics approaches

Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites

Metabolomics in pesticide research and development: review and future perspectives

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