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Temperature shift activates bloodstream VSG expression site promoters in Trypanosoma brucei.

ABSTRACT: Trypanosoma brucei relies on two types of variant surface glycoprotein (VSG) expression sites (ESs) for RNA polymerase I (Pol I) transcription of VSG pre-mRNA. Trypanosomes developing into infectious metacyclic cells in the tsetse vector use metacyclic VSG ESs (MESs) and proliferating parasites in the mammalian host deploy bloodstream VSG ESs (BESs). Unlike the monocistronic MESs, BESs are polycistronic and their highly conserved promoters differ considerably from the MES promoters. The significance of the divergent sequences of MES and BES promoters remains to be determined. We used a reporter system to specifically test the effect of temperature on the activity of MES and BES promoters in procyclic trypanosomes and our results demonstrate that transcription from the MES promoter is largely insensitive to changes in temperature. In contrast, the BES promoter drives rapid activation of transcription upon a change of temperature from 28?°C to 37?°C. Additionally, endogenous BESs respond similarly to the elevation of temperature and initiate increased production of BES pre-mRNA and mRNA. Our results indicate that the sequence of the BES promoter is a specificity signal which triggers BES activation in vivo upon entry into the mammalian host.

SUBMITTER: Kolev NG

PROVIDER: S-EPMC6258174 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Temperature shift activates bloodstream VSG expression site promoters in Trypanosoma brucei.

Kolev Nikolay G NG Ramsdell Trisha K TK Tschudi Christian C

Molecular and biochemical parasitology 20181103

Trypanosoma brucei relies on two types of variant surface glycoprotein (VSG) expression sites (ESs) for RNA polymerase I (Pol I) transcription of VSG pre-mRNA. Trypanosomes developing into infectious metacyclic cells in the tsetse vector use metacyclic VSG ESs (MESs) and proliferating parasites in the mammalian host deploy bloodstream VSG ESs (BESs). Unlike the monocistronic MESs, BESs are polycistronic and their highly conserved promoters differ considerably from the MES promoters. The signific ...[more]

PMID: 30399391

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Project description:Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs) by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs) we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES). Thus, Expression Site Associated Genes (ESAGs) sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR), expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf) uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection supporting previous epidemiological results.

Dataset Information

Temperature shift activates bloodstream VSG expression site promoters in Trypanosoma brucei.

Publications

Temperature shift activates bloodstream VSG expression site promoters in Trypanosoma brucei.

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