ArticlePLoS neglected tropical diseases2020
Intracellular DNA replication and differentiation of Trypanosoma cruzi is asynchronous within individual host cells in vivo at all stages of infection.
Article in PLoS neglected tropical diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- A Rapid Method for Purifying Intact Trypanosoma cruzi Amastigotes from Host Cells, In Vitro and In Vivo, for Downstream 'Omic Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.Clinical microbiology reviews · 2024Review
- Retrospect, advances and challenges in Chagas disease diagnosis: a comprehensive review.Lancet regional health. Americas · 2024Review
- A panel of phenotypically and genotypically diverse bioluminescent:fluorescent Trypanosoma cruzi strains as a resource for Chagas disease research.PLoS neglected tropical diseases · 2024Article
- The End Justifies the Means: Chagas Disease from a Perspective of the Host-Life (Basel, Switzerland) · 2024Review
- Trypanosoma cruzi interaction with host tissues modulate the composition of large extracellular vesicles.Scientific reports · 2024Article
- Metacyclogenesis as the Starting Point of Chagas Disease.International journal of molecular sciences · 2023Review
- Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice.PLoS pathogens · 2023Article
- Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy.Journal of clinical medicine · 2023Article
- Impact of Laboratory-Adapted IntracellularMicroorganisms · 2023Article
- Collaborative Virtual Screening Identifies a 2-Aryl-4-aminoquinazoline Series with Efficacy in anJournal of medicinal chemistry · 2023Article
- Unveiling challenges in real-time PCR strategies for detecting treatment failure: observations from clinical trials on chronic Chagas disease.Frontiers in parasitology · 2023Review
- Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy.Microbiology spectrum · 2022Article
- Sheltered in Stromal Tissue Cells,Pathogens (Basel, Switzerland) · 2022Article
- Host-parasite dynamics in Chagas disease from systemic to hyper-local scales.Parasite immunology · 2021Review
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Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Investigations into intracellular replication and differentiation of Trypanosoma cruzi within the mammalian host have been restricted by limitations in our ability to detect parasitized cells throughout the course of infection. We have overcome this problem by generating genetically modified parasites that express a bioluminescent/fluorescent fusion protein. By combining in vivo imaging and confocal microscopy, this has enabled us to routinely visualise murine infections at the level of individual host cells. These studies reveal that intracellular parasite replication is an asynchronous process, irrespective of tissue location or disease stage. Furthermore, using TUNEL assays and EdU labelling, we demonstrate that within individual infected cells, replication of both mitochondrial (kDNA) and nuclear genomes is not co-ordinated within the parasite population, and that replicating amastigotes and non-replicating trypomastigotes can co-exist in the same cell. Finally, we report the presence of distinct non-canonical morphological forms of T. cruzi in the mammalian host. These appear to represent transitional forms in the amastigote to trypomastigote differentiation process. Therefore, the intracellular life-cycle of T. cruzi in vivo is more complex than previously realised, with potential implications for our understanding of disease pathogenesis, immune evasion and drug development. Dissecting the mechanisms involved will be an important experimental challenge.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.