A quorum sensing-independent path to stumpy development in Trypanosoma brucei.

Henriette Zimmermann,Markus Engstler,Christian J Janzen,Ines Subota,Christopher Batram,Nicola G Jones,Susanne Kramer,Samuel James Black

doi:10.1371/journal.ppat.1006324

Henriette Zimmermann, Markus Engstler + Show 6 more

Open Access

https://doi.org/10.1371/journal.ppat.1006324

Copy DOI

Journal: PLoS pathogens	Publication Date: Apr 10, 2017
Citations: 35	License type: CC BY 4.0

Affiliation: University of Würzburg

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.

Highlights

Pathogenic bacteria and protozoan parasites often employ a coat of surface molecules to protect themselves from host immune attack
variant surface glycoprotein (VSG) are expressed from a specialized region in the genome, the expression site (ES), that contains essential expression site associated genes (ESAGs)
It was assumed that only successful antigenic switches to an intact expression site are viable

Summary

Introduction

Pathogenic bacteria and protozoan parasites often employ a coat of surface molecules to protect themselves from host immune attack. These surface coats are sometimes variable and act as a physical shield but have evolved as an efficient camouflage strategy. The surface-exposed proteins are mostly members of large families and are subject to antigenic variation, i.e. they are sporadically exchanged. This allows the persistence of the pathogens in the host, as well as reinfection. At all times the parasite has to maintain the shielding function of the coat and the concentration of VSGs on the cell surface. This high level expression of VSG is driven by RNApolymerase I [9]

Methods

Results

Discussion

Conclusion