Slow growing behavior in African trypanosomes during adipose tissue colonization

Sandra Trindade, Mariana Niz, Mariana Costa-Sequeira, Tiago Bizarra-Rebelo, Fábio Bento, Mario Dejung, Marta Valido Narciso, Lara López-Escobar, João Ferreira, Falk Butter, Frédéric Bringaud, Erida Gjini () and Luisa M. Figueiredo ()
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Sandra Trindade: Universidade de Lisboa
Mariana Niz: Universidade de Lisboa
Mariana Costa-Sequeira: Universidade de Lisboa
Tiago Bizarra-Rebelo: Universidade de Lisboa
Fábio Bento: Universidade de Lisboa
Mario Dejung: Institute of Molecular Biology
Marta Valido Narciso: Universidade de Lisboa
Lara López-Escobar: Universidade de Lisboa
João Ferreira: Universidade de Lisboa
Falk Butter: Institute of Molecular Biology
Frédéric Bringaud: Université de Bordeaux, CNRS
Erida Gjini: Instituto Gulbenkian de Ciência
Luisa M. Figueiredo: Universidade de Lisboa

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34622-w

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