ArticleAntimicrobial agents and chemotherapy2013
Metabolomics guides rational development of a simplified cell culture medium for drug screening against Trypanosoma brucei.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 99 citations in OpenAlex.
- Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions.Nature communications · 2026Article
- A genome-wide genetic screen identifies a novel kDNA replication protein in trypanosomes.Nucleic acids research · 2026Article
- Differentiation granules, a dynamic regulator of T. brucei development.Nature communications · 2024Article
- The bloodstream form of Trypanosoma brucei displays non-canonical gluconeogenesis.PLoS neglected tropical diseases · 2024Article
- Multiparameter ranking of carbazoles for anti-trypanosome lead discovery.Frontiers in drug discovery · 2024Article
- Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation.PLoS pathogens · 2023Article
- Cell-cell communication in African trypanosomes.Microbiology (Reading, England) · 2023Review
- How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell.PLoS pathogens · 2023Article
- Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.Metabolomics : Official journal of the Metabolomic Society · 2022Review
- A novel lipase with dual localisation in Trypanosoma brucei.Scientific reports · 2022Article
- Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast.eLife · 2021Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs.PLoS pathogens · 2020Article
- Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery.Genes · 2020Review
- Metabolomics technology and bioinformatics for precision medicine.Briefings in bioinformatics · 2019Review
- Metabolomics, lipidomics and proteomics profiling of myoblasts infected with Trypanosoma cruzi after treatment with different drugs against Chagas disease.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Mapping the metabolism of five amino acids in bloodstream formBioscience reports · 2019Article
- Article
- Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions.PLoS pathogens · 2018Article
- Insights into antitrypanosomal drug mode-of-action from cytology-based profiling.PLoS neglected tropical diseases · 2018Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
In vitro culture methods underpin many experimental approaches to biology and drug discovery. The modification of established cell culture methods to make them more biologically relevant or to optimize growth is traditionally a laborious task. Emerging metabolomic technology enables the rapid evaluation of intra- and extracellular metabolites and can be applied to the rational development of cell culture media. In this study, untargeted semiquantitative and targeted quantitative metabolomic analyses of fresh and spent media revealed the major nutritional requirements for the growth of bloodstream form Trypanosoma brucei. The standard culture medium (HMI11) contained unnecessarily high concentrations of 32 nutrients that were subsequently removed to make the concentrations more closely resemble those normally found in blood. Our new medium, Creek's minimal medium (CMM), supports in vitro growth equivalent to that in HMI11 and causes no significant perturbation of metabolite levels for 94% of the detected metabolome (<3-fold change; α = 0.05). Importantly, improved sensitivity was observed for drug activity studies in whole-cell phenotypic screenings and in the metabolomic mode of action assays. Four-hundred-fold 50% inhibitory concentration decreases were observed for pentamidine and methotrexate, suggesting inhibition of activity by nutrients present in HMI11. CMM is suitable for routine cell culture and offers important advantages for metabolomic studies and drug activity screening.
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