ArticleProceedings of the National Academy of Sciences of the United States of America2006
Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 85 citations in OpenAlex.
- Outlining the structure of cAMP compartments in Trypanosoma cruzi.Trends in parasitology · 2025Review
- Adhesion ofmSphere · 2024Article
- The ElusivePathogens (Basel, Switzerland) · 2023Review
- VEX1 Influences mVSG Expression During the Transition to Mammalian Infectivity inFrontiers in cell and developmental biology · 2022Article
- An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation ineLife · 2020Article
- A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies.Nature communications · 2020Article
- Evaluation of Modulators of cAMP-Response in Terms of Their Impact on Cell Cycle and Mitochondrial Activity ofFrontiers in pharmacology · 2020Article
- Review
- Developmental competence and antigen switch frequency can be uncoupled inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- African trypanosomes.Parasites & vectors · 2019Article
- Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma.Nature communications · 2019Article
- Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.International journal of molecular sciences · 2019Review
- The suppressive cap-binding complex factor 4EIP is required for normal differentiation.Nucleic acids research · 2018Article
- Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes.PLoS pathogens · 2018Article
- Adenylate Cyclases ofPathogens (Basel, Switzerland) · 2018Review
- Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential.Nature microbiology · 2017Article
- The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream.Pathogens (Basel, Switzerland) · 2017Review
- Reactivation of flagellar motility in demembranated Leishmania reveals role of cAMP in flagellar wave reversal to ciliary waveform.Scientific reports · 2016Article
- The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei.Cell reports · 2016Article
- An Overview ofFrontiers in microbiology · 2016Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
African sleeping sickness is a disease caused by Trypanosoma brucei. T. brucei proliferate rapidly in the mammalian bloodstream as long, slender forms, but at higher population densities they transform into nondividing, short, stumpy forms. This is thought to be a mechanism adopted by T. brucei to establish a stable host-parasite relationship and to allow a transition into the insect stage of its life cycle. Earlier studies have suggested a role for cAMP in mediating this transformation. In this study, using membrane-permeable nucleotide analogs, we show that it is not the cAMP analogs themselves but rather the hydrolyzed products of membrane-permeable cAMP analogs that prevent proliferation of T. brucei. The metabolic products are more potent than the cAMP analogs, and hydrolysis-resistant cAMP analogs are not antiproliferative. We further show that the antiproliferative effect of these membrane-permeable adenosine analogs is caused by transformation into forms resembling short, stumpy bloodstream forms. These data suggest that the slender-to-stumpy transformation of T. brucei may not be mediated directly by cAMP and also raise the possibility of using such adenosine analogs as antitrypanosomal drugs.
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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.