Slow growing behavior in African trypanosomes during adipose tissue colonization

• Published in: Nature communications Vol. 13; no. 1; pp. 7548 - 13
• Main Authors: Trindade, Sandra, De Niz, Mariana, Sequeira, Mariana, Rebelo, Tiago, Bento, Fabio, Dejung, Mario, Valido Narciso, Marta, Escobar, Lara, Ferreira, João, Butter, Falk, Bringaud, Frédéric, Gjini, Erida, Figueiredo, Luisa M
• Format: Journal Article
• Language: English
• Published: London Springer Nature 08-12-2022; Nature Publishing Group UK; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 14/19; 38; 38/22; 38/39; 38/77; 38/88; 59; 631/326/417/1716; 631/80/304; 64; 82/58; Adipose Tissue; African trypanosomiasis; Biochemistry, Molecular Biology; Blood; Blood parasites; Body fat; Central nervous system; Colonization; Gene expression; Genomics; Humanities and Social Sciences; Life Sciences; Mathematical analysis; Mathematical models; Medical treatment; Microbiology and Parasitology; multidisciplinary; Parasites; Parasitology; Protein biosynthesis; Protein synthesis; Proteomes; Protozoa; Science; Science (multidisciplinary); Trypanosoma brucei; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34622-w

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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.
The project leading to this application has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 771714). This work was also supported by IC&DT Programa de Actividades Conjuntas – ref. 016417 “Oneida”, PTDC/BIMMET/4471/2014 and PTDC/CVT-CVT/29161/2017 (FCT). SFRH/BPD/89833/2012 and DL 57/2016/CP1451/CT0019 (FCT) to S.T, LT000047/2019-L (HFSP) and ALTF 1048-2016 (EMBO) to M.D.N, MSCA ITN Cell2Cell fellowship to L.LE and CEECIND/03322/2018 (FCT) to L.M.F. FBr is supported by the Agence National de Recherche (ANR, grant number ANR19-CE15-0004-01: ADIPOTRYP), the Fondation pour le Recherche Médicale (FRM, grant n°EQU201903007845: “Equipe FRM”) and the Laboratoire d’Excellence (grant number ANR-11-LABX-0024:ParaFrap).