ArticlePloS one2014
Proline modulates the Trypanosoma cruzi resistance to reactive oxygen species and drugs through a novel D, L-proline transporter.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Energy metabolism inmBio · 2025Review
- Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline.PLoS neglected tropical diseases · 2024Article
- Genomic surveillance: a potential shortcut for effective Chagas disease management.Memorias do Instituto Oswaldo Cruz · 2023Article
- An Update on African Trypanocide Pharmaceutics and Resistance.Frontiers in veterinary science · 2022Review
- Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis inMolecules (Basel, Switzerland) · 2020Article
- Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development.Frontiers in chemistry · 2020Article
- Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses.Memorias do Instituto Oswaldo Cruz · 2020Article
- Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069.PLoS neglected tropical diseases · 2020Article
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
- Article
- Characterisation of a putative glutamate 5-kinase from Leishmania donovani.The FEBS journal · 2018Article
- The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids.Pathogens (Basel, Switzerland) · 2018Review
- Metabolomic profiling for the identification of potential biomarkers involved in a laboratory azole resistance in Candida albicans.PloS one · 2018Article
- Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch inThe Journal of biological chemistry · 2017Article
- Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi.PLoS neglected tropical diseases · 2017Article
- Quantitative Laser Biospeckle Method for the Evaluation of the Activity of Trypanosoma cruzi Using VDRL Plates and Digital Analysis.PLoS neglected tropical diseases · 2016Article
- The active transport of histidine and its role in ATP production in Trypanosoma cruzi.Journal of bioenergetics and biomembranes · 2016Article
- Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation.Oncotarget · 2016Article
- Article
- Phylogenetic and syntenic data support a single horizontal transference to a Trypanosoma ancestor of a prokaryotic proline racemase implicated in parasite evasion from host defences.Parasites & vectors · 2015Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma cruzi, the etiological agent of Chagas' disease, has a metabolism largely based on the consumption of glucose and proline. This amino acid is essential for host cells infection and intracellular differentiation. In this work we identified a proline transporter (TcAAAP069) by yeasts complementation assays and overexpression in Trypanosoma cruzi epimastigotes. TcAAAP069 is mono-specific for proline but presents an unusual feature; the lack of stereospecificity, because it is competitively inhibited by the D- enantiomer. Parasites overexpressing TcAAAP069 have an increased intracellular proline concentration, 2.6-fold higher than controls, as a consequence of a higher proline transport rate. Furthermore, augmented proline concentration correlates with an improved resistance to trypanocidal drugs and also to reactive oxygen species including hydrogen peroxide and nitric oxide, emulating natural physiological situations. The IC50s for nifurtimox, benznidazole, H2O2 and NO. were 125%, 68%, 44% and 112% higher than controls, respectively. Finally, proline metabolism generates a higher concentration (48%) of ATP in TcAAAP069 parasites. Since proline participates on essential energy pathways, stress and drug resistance responses, these results provide a novel target for the development of new drugs for the treatments for Chagas' disease.
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