Slow growing behavior in African trypanosomes during adipose tissue colonization

When Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure. Trypanosoma brucei parasites invade different organs, such as the central nervous system, adipose tissue, and skin in mammalian host. Here, Trindade et al. perform mathematical modelling to show that adipose tissue forms (ATFs) grow slower than the bloodstream forms and experimentally characterize the heterogeneous ATF populations and provide evidence that slow-growing forms are refractory to drug treatment.