A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in...

Area of Science:

• Parasitology
• Molecular Biology
• Cell Biology

Background:

• Trypanosomatid parasites, including Trypanosoma congolense, exhibit developmental regulation for life cycle adaptation.
• A regulator, TbREG9.1, from Trypanosoma brucei, has an orthologue (TcREG9.1) in Trypanosoma congolense, despite the latter lacking a stumpy morphotype.
• Trypanosomiasis is a significant cause of livestock disease.

Purpose of the Study:

• To investigate the function of TcREG9.1 in Trypanosoma congolense.
• To understand the role of TcREG9.1 in parasite attachment, development, and transmission.

Main Methods:

• RNA interference (RNAi) mediated gene silencing of TcREG9.1.
• In vitro assays measuring parasite attachment to substrates.
• Phenotypic analysis including phosphodiesterase inhibitor treatment.
• RNA sequencing (RNAseq) to analyze gene expression changes.
• In vivo studies to assess parasite levels and attachment.

Main Results:

• TcREG9.1 gene silencing led to parasite detachment from surfaces in vitro.
• Detachment was mimicked by phosphodiesterase inhibitor treatment.
• RNAseq revealed upregulation of surface molecule mRNAs, including transferrin receptor-like molecules.
• In vivo depletion of TcREG9.1 resulted in increased parasitemia due to reduced microvasculature attachment.
• Parasite morphological progression to insect forms was disrupted.

Conclusions:

• TcREG9.1 functions as a key regulator of attachment and development in Trypanosoma congolense.
• Detached parasites, regulated by TcREG9.1, are potentially adapted for transmission.
• This finding offers insights into the biology of livestock trypanosomiasis and parasite transmission.