Persistence behavior in African trypanosomes during adipose tissue colonization

Abstract Persistence is an important and ancient evolutionary adaptive mechanism used by several organisms to survive environmental changes. During its life cycle Trypanosoma brucei, the causative agent of sleeping sickness, inhabits several microenvironments, including the adipose tissue. Here we used a mathematical model to investigate how this large parasite reservoir contributes to the global parasite population dynamics. By modeling the total number of parasites and the proportion of transmissible forms in the blood and the adipose tissue during an infection, we estimated that adipose tissue parasites proliferate more slowly. Intravital microscopy of parasites stained with CellTraceTM Violet confirmed that adipose tissue forms divide twice slower than the blood counterparts. Consistent with a reduced growth, proteome analysis revealed that adipose tissue forms undergo a metabolic adaptation and downregulate proteins involved in translation. Quantification of protein synthesis using L-Homopropargylglycine confirmed that this rate is 24% lower in adipose tissue forms. We propose that in adipose tissue, T. brucei acquire a persistence-like behavior, which could contribute to disease chronicity and treatment failure.