An Alternative Strategy for Trypanosome Survival in the Mammalian Bloodstream Revealed through Genome and Transcriptome Analysis of the Ubiquitous Bovine Parasite Trypanosoma (Megatrypanum) theileri

Abstract

There are hundreds of Trypanosoma species that live in the blood and tissue spaces of their vertebrate hosts. The vast majority of these do not have the ornate system of antigenic variation that has evolved in the small number of African trypanosome species, but can still maintain long-term infections in the face of the vertebrate adaptive immune system. Trypanosoma theileri is a typical example, has a restricted host range of cattle and other Bovinae, and is only occasionally reported to cause patent disease although no systematic survey of the effect of infection on agricultural productivity has been performed. Here, a detailed genome sequence and a transcriptome analysis of gene expression in bloodstream form T. theileri have been performed. Analysis of the genome sequence and expression showed that T. theileri has a typical kinetoplastid genome structure and allowed a prediction that it is capable of meiotic exchange, gene silencing via RNA interference and, potentially, density-dependent growth control. In particular, the transcriptome analysis has allowed a comparison of two distinct trypanosome cell surfaces, T. brucei and T. theileri, that have each evolved to enable the maintenance of a long-term extracellular infection in cattle. The T. theileri cell surface can be modeled to contain a mixture of proteins encoded by four novel large and divergent gene families and by members of a major surface protease gene family. This surface composition is distinct from the uniform variant surface glycoprotein coat on African trypanosomes providing an insight into a second mechanism used by trypanosome species that proliferate in an extracellular milieu in vertebrate hosts to avoid the adaptive immune response.

Targeting tRNA-Synthetase Interactions towards Novel Therapeutic Discovery Against Eukaryotic Pathogens

“…To compare CIFs between TriTrypDB genomes and humans and to have sufficient data to estimate CIFs, we defined eight phylogenetic clades for 40 of the 46 trypanosome genomes as shown in Table 1. These clades were based on a composite of phylogenetic results in the literature [44-47] and CIFs were subsequently analyzed independently by clade. We removed two incomplete genomes from analysis, T. rangeli SC58 and T. cruzi CLBrenner that had fewer than half the number of tRNA genes identified in any other genome.…”

Transcriptional and genomic parallels between the monoxenous parasiteHerpetomonas muscarumandLeishmania

“…The following proteomes were inputted into the Orthofinder script; Trypanosoma brucei brucei 927 v5.1 (Berriman et al, 2005), Trypanosoma brucei gambiense DAL972 v3 (Jackson et al ., 2010), Trypanosoma congolense IL3000 (Jackson et al ., 2012), Trypanosoma cruzi (CL Brener) (El-Sayed et al ., 2005), Trypanosoma evansi STIB805 (Carnes et al ., 2015), Trypanosoma grayi ANR4 v1 (Kelly et al ., 2015), Trypanosoma rangeli SC_58 v1 (Stoco et al ., 2014), Trypanosoma theileri Edinburgh (Kelly et al ., 2017), Trypanosoma vivax Y486 (Jackson et al ., 2012), Leishmania braziliensis M2903 (Peacock et al ., 2007), Leishmania donovani BPK282 v1 (Downing et al ., 2011), Leishmania infantum JPCM5 (Peacock et al ., 2007), Leishmania major Friedlin v6 (Ivens et al ., 2005), Leptomonas pyrrhocoris ASM129339v1 (Flegontov et al ., 2016), Leptomonas seymori ASM129953v1 (Kraeva et al ., 2015), Crithidia bombi (Schmid-Hempel et al ., 2018), Crithidia expoeki (Schmid-Hempel et al ., 2018), Crithidia fasciculata v14.0 (Runkel et al ., 2014), Angomonas deanei (Motta et al ., 2013), Phytomonas FM1 (Porcel et al ., 2014) and Bodo saltans v3 (Jackson et al ., 2008). Where possible the above sequences were obtained from TriTrypDB v41 (Aslett et al ., 2010).…”

Evolution of Antigenic Variation in African Trypanosomes: Variant Surface Glycoprotein Expression, Structure, and Function

“…For instance, T. cruzi has a complex glycocalyx composed of multiple monomeric GPI‐anchored proteins and free GPI lipids, perhaps reflecting the fact that T. cruzi is a mostly intracellular parasite that is only transiently exposed to host immunity . However, this may be overly simplistic as T. theileri , which is more closely related to T. cruzi , is modeled to have a similarly complex glycocalyx, yet is exclusively an extracellular parasite in the bovine host . That T. theileri also establishes long‐term infections indicates there are strategic alternatives to the paradigm of antigenic variation seen in African trypanosomes.…”

“…Already from the available genomic and transcriptomic data it is clear that both species differ significantly in their approach to antigenic variation. T. vivax diverged closer to the evolutionary root of the African trypanosomes, while the split of T. brucei and T. congolense is a more recent event . Illuminating this issue in these species will without doubt significantly impact our understanding of the evolution of antigenic variation in T. brucei .…”