# Trypanosoma brucei cattle infections contain cryptic transmission-adapted bloodstream forms at low parasitaemia

## TL;DR

The study finds that Trypanosoma brucei in cattle have mixed parasite forms at low blood parasite levels, challenging previous assumptions based on rodent models.

## Contribution

The research reveals host-specific metabolic adaptations and mixed transcriptomic profiles in cattle, challenging rodent-based assumptions about parasite development.

## Key findings

- Cattle blood contains mixed parasite populations with both slender- and stumpy-like transcriptomes at low parasitaemia.
- Parasites in cattle show metabolic adaptations like upregulated pyruvate and TCA cycle transcripts in slender-like forms.
- Transcriptomic signatures are conserved between cattle and rodents, but host-specific differences are also observed.

## Abstract

Tsetse-transmitted Trypanosoma parasites infect a wide host range and cause Human African Trypanosomiasis and Animal African Trypanosomosis. The dominant hosts of Trypanosoma brucei sensu lato are non-human mammals, including agriculturally important cattle. In rodent infections, T. brucei transitions from proliferative slender to tsetse-transmissible stumpy forms at high parasitaemia in a density-dependent quorum sensing-type process. However, chronic bovine infections are characterised by markedly lower blood parasitaemia levels; mostly substantially below the density assumed to trigger slender-to-stumpy differentiation. This challenges the current (rodent-based) assumptions and quantitative parameter estimations around stumpy form generation in the bloodstream. By combining scRNA-seq and microscopy we observe mixed populations of parasites with both slender- and stumpy-associated transcriptomes in cattle blood. The appearance of the latter coincides with fewer detectably dividing parasites and parasites with shortened flagellum indicative of differentiation, despite the absence of stumpy morphology or developmental marker protein expression. Comparisons with murine infections and in vitro culture demonstrates conserved transcriptomic signatures for both slender- and stumpy-like forms, as well as host specific differences, including a subpopulation of slender-like parasites upregulating pyruvate metabolism and TCA cycle transcripts in cattle samples. These similarities and differences are key to understanding parasite development and transmission in its natural host.

Trypanosoma brucei parasites in cattle show mixed transcriptomic profiles at low parasitaemia, challenging rodent-based models of parasite development and revealing host-specific metabolic adaptations key to transmission.