Abstract
BackgroundDuring natural Trypanosoma brucei infections, the parasites differentiate spontaneously into a non-dividing “stumpy” form when a certain level of parasitaemia is attained. This form is metabolically adapted for rapid further differentiation into procyclic forms upon uptake by Tsetse flies.ResultsWe describe here four central Ugandan isolates of Trypanosoma brucei rhodesiense that have undergone only three rodent passages since isolation from human patients. As expected, SNP analysis shows that these isolates are more closely related to each other than to the commonly used strains Lister 427, Antat1.1, and TREU927. TREU927 generally has smaller copy numbers of repeated genes than the other strains, while Lister 427 trypanosomes with a 30-year history of in vitro culture and cloning have more histone genes than the other isolates. The recently isolated trypanosomes were grown in rats, and their transcriptomes characterised. In comparison with cultured procyclic and bloodstream forms, there were increases in mRNAs encoding the stumpy-form markers ESAG9 and PIP39, with coordinated alterations in the levels of over 600 additional mRNAs. Numerous mRNAs encoding proteins of no known function were either increased or decreased. The products of the mRNAs that were increased in parallel with PIP39 included not only enzymes of procyclic-form metabolism, but also components of the translational and RNA control machineries. Many of the mRNAs that were decreased in cells with elevated PIP39 reflected reduced cell division.ConclusionsThese transcriptomes suggest new avenues for research into the regulation of trypanosome differentiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2338-y) contains supplementary material, which is available to authorized users.
Highlights
During natural Trypanosoma brucei infections, the parasites differentiate spontaneously into a non-dividing “stumpy” form when a certain level of parasitaemia is attained
Disease in humans is caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, both of which are resistant to the trypanolytic factors
When mice are infected with trypanosomes that can undergo stumpy differentiation (“pleomorphic” lines), there is an initial rise in parasites, which flattens out as stumpy differentiation occurs; trypanosomes disappear from the blood as an immune response develops to the variant surface glycoprotein (VSG)
Summary
The four new isolates cause chronic infections in mice New T. rhodesiense isolates from human patients were tested for infectiveness for mice. A comparison of their transcriptomes [30] with those of bloodstream and procyclic forms revealed 126 increased mRNAs that were elevated in the LW032 and LW042 transcriptomes (Additional file 5: Table S4, sheet 6) These included the two cell-cycle RNAs mentioned above, and mRNAs encoding the RNA-binding protein RBP5, a protein kinase and two chaperones. 100 genes showed at least 3-fold less mRNA in all of the blood trypanosomes relative to cultured bloodstream- or procyclic-form Lister 427 (Additional file 5: Table S4, sheet 6). They included PUF9, the product of which stabilises S-phase mRNAs, and one of its target mRNAs, PNT1 [35]. Twenty-two of them were under-represented in salivary gland trypanosome RNA; these included PUF2, PUF4, ZC3H8, PIE8 and several encoding proteins implicated in signal transduction
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