ArticleProceedings of the National Academy of Sciences of the United States of America2019
Developmental competence and antigen switch frequency can be uncoupled in
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Mechanisms of life cycle simplification in African trypanosomes.Nature communications · 2024Article
- Differentiation granules, a dynamic regulator of T. brucei development.Nature communications · 2024Article
- The developmental hierarchy and scarcity of replicative slender trypanosomes in blood challenges their role in infection maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei.Molecular microbiology · 2021Review
- The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.Nucleic acids research · 2021Article
- The Occurrence of Malignancy inFrontiers in microbiology · 2021Article
- Developmental competence and antigen switch frequency can be uncoupled inProceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
African trypanosomes use an extreme form of antigenic variation to evade host immunity, involving the switching of expressed variant surface glycoproteins by a stochastic and parasite-intrinsic process. Parasite development in the mammalian host is another feature of the infection dynamic, with trypanosomes undergoing quorum sensing (QS)-dependent differentiation between proliferative slender forms and arrested, transmissible, stumpy forms. Longstanding experimental studies have suggested that the frequency of antigenic variation and transmissibility may be linked, antigen switching being higher in developmentally competent, fly-transmissible, parasites ("pleomorphs") than in serially passaged "monomorphic" lines that cannot transmit through flies. Here, we have directly tested this tenet of the infection dynamic by using 2 experimental systems to reduce pleomorphism. Firstly, lines were generated that inducibly lose developmental capacity through RNAi-mediated silencing of the QS signaling machinery ("inducible monomorphs"). Secondly, de novo lines were derived that have lost the capacity for stumpy formation by serial passage ("selected monomorphs") and analyzed for their antigenic variation in comparison to isogenic preselected populations. Analysis of both inducible and selected monomorphs has established that antigen switch frequency and developmental capacity are independently selected traits. This generates the potential for diverse infection dynamics in different parasite populations where the rate of antigenic switching and transmission competence are uncoupled. Further, this may support the evolution, maintenance, and spread of important trypanosome variants such as
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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.