Research Article: Global Gene Expression Profiling through the Complete Life Cycle of Trypanosoma vivax

Date Published: August 12, 2015

Publisher: Public Library of Science

Author(s): Andrew P. Jackson, Sophie Goyard, Dong Xia, Bernardo J. Foth, Mandy Sanders, Jonathan M. Wastling, Paola Minoprio, Matthew Berriman, Philippe Büscher.

Abstract: The parasitic flagellate Trypanosoma vivax is a cause of animal trypanosomiasis across Africa and South America. The parasite has a digenetic life cycle, passing between mammalian hosts and insect vectors, and a series of developmental forms adapted to each life cycle stage. Each point in the life cycle presents radically different challenges to parasite metabolism and physiology and distinct host interactions requiring remodeling of the parasite cell surface. Transcriptomic and proteomic studies of the related parasites T. brucei and T. congolense have shown how gene expression is regulated during their development. New methods for in vitro culture of the T. vivax insect stages have allowed us to describe global gene expression throughout the complete T. vivax life cycle for the first time. We combined transcriptomic and proteomic analysis of each life stage using RNA-seq and mass spectrometry respectively, to identify genes with patterns of preferential transcription or expression. While T. vivax conforms to a pattern of highly conserved gene expression found in other African trypanosomes, (e.g. developmental regulation of energy metabolism, restricted expression of a dominant variant antigen, and expression of ‘Fam50’ proteins in the insect mouthparts), we identified significant differences in gene expression affecting metabolism in the fly and a suite of T. vivax-specific genes with predicted cell-surface expression that are preferentially expressed in the mammal (‘Fam29, 30, 42’) or the vector (‘Fam34, 35, 43’). T. vivax differs significantly from other African trypanosomes in the developmentally-regulated proteins likely to be expressed on its cell surface and thus, in the structure of the host-parasite interface. These unique features may yet explain the species differences in life cycle and could, in the form of bloodstream-stage proteins that do not undergo antigenic variation, provide targets for therapy.

Partial Text: African trypanosomes are unicellular vector-borne hemoparasites of humans, domestic livestock and wild animals. They cause African trypanosomiasis, an endemic disease of sub-Saharan Africa otherwise known as sleeping sickness in humans and nagana in animals, and are transmitted between vertebrate hosts by the bite of tsetse flies (Glossina spp.). This endemic disease causes considerable morbidity in livestock herds and associated losses in animal productivity. The threat of Animal African trypanosomiasis in tsetse-infested areas also prevents effective exploitation of available pasture, thereby impeding economic development in the world’s poorest nations.

We have produced transcriptomes and proteomes for three different developmental forms of T. vivax, and identified the transcripts and peptides that are significantly enriched in each. These data provide the first profile of global gene expression and developmental regulation throughout the complete T. vivax life cycle. The profile suggests a situation broadly similar to that already observed in T. brucei and T. congolense, though with significant distinctions, not least further evidence for developmental regulation of species-specific cell surface glycoproteins in both the vertebrate and insect stages of T. vivax.



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