title: A quorum sensing-independent path to stumpy development in Trypanosoma brucei.
abstract: For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Ines
authors.identifier: http://orcid.org/0000-0002-2465-0599
authors.initials: I
authors.lastname: Subota
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Batram
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kramer
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Janzen
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Nicola G
authors.identifier: http://orcid.org/0000-0003-3384-0156
authors.initials: NG
authors.lastname: Jones
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Engstler
mesh_terms: D000818:Animals; D000940:Antigenic Variation / Q000276:immunology*; D002454:Cell Differentiation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008322:Mammals; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053038:Quorum Sensing / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000276:immunology; D014370:Tsetse Flies / Q000469:parasitology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D014643:Variant Surface Glycoproteins, Trypanosoma