African trypanosomes, the causative agents of sleeping sickness (Trypanosoma brucei) and nagana (Trypanosoma congolense), experience host-derived increases intemperature, due to the prominent mammalian symptom of fever during infection. In response, these parasites activate a heat shock (HS) response that promotes survival under elevated temperatures. This work aimed to characterise the HS response in T.brucei, with preliminary comparative analysis in T. congolense. The results show that T. brucei immediately responds to a 1 hour 41 °C HS with a lag in cell growth lasEng around 24 hours, influenced by a HS-induced reversible cell cycle arrest observed as an enrichment of G2M cells, which was resolved following around 8 hours of recovery. Immediately aLer HS in T. brucei an increase in DHH1 foci occurred, interpreted as the formaEon of P-bodies, alongside the collapse in polysomes. The collapse in polysomes reflects the state of global translaEonal arrest, through the decrease in acEve translaEonal machinery via a decrease in polysomes and an increase in ribosomal subunits. Polysome collapse in T. brucei post-HS was viewed as being more severe in procyclic form cells than bloodstream form cells, potenEally indicaEng differences in thermotolerance across the cell cycle. Polysome analysis in T. congolense also found a decrease in polysomes post-HS, also presenEng an increase in ribosomal instability as observed in T. brucei, indicaEng a level of conservaEon in the two species’ HS response. Understanding the HS response in trypanosomes is crucial for uncovering parasite survival strategies under host-induced stress and may highlight unique regulatory pathways absent in mammalian hosts. These insights offer potential avenues for future targeted therapeutic development; potential common targets in T. brucei and T. congolense are of interest due to their ability to co-infect the same hosts and their exposure to similar selective pressures
Hannah Pyle (Thu,) studied this question.