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.
Highlights
African trypanosomes are unicellular vector-borne hemoparasites of humans, domestic livestock and wild animals
We present an analysis of gene expression throughout the T. vivax life cycle that compares the abundance of gene transcripts and proteins in the mammalian and insect hosts
We have identified genes that are preferentially expressed in each life stage, including many that are unique to T. vivax and probably expressed on its cell surface
Summary
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.). Trypanosoma brucei is predominantly an animal pathogen that has evolved the ability to infect humans on multiple occasions [1], while T. congolense and T. vivax are exclusively animal pathogens During their life cycles, T. brucei and T. congolense exist as procyclic forms in the mid-gut of the tsetse fly before migrating into the salivary glands and proventriculus respectively, where they develop into epimastigotes and metacyclic trypomastigotes that are able to infect vertebrates (see Fig 1). This difference might explain why T. vivax can be transmitted by other kinds of biting insect [3,4] and has spread beyond the sub-Saharan distribution of the tsetse fly into northern Africa and South America [5,6]
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