18 documents found, page 1 of 2
m6A landscape is more pervasive when Trypanosoma brucei exits the cell cycle
Serra, Lúcia; Pereira, Sara Silva; Viegas, Idálio J.; Machado, Henrique; López-Escobar, Lara; Figueiredo, Luisa M.N6-methyladenosine (m6A) is an mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts, and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m6A landscape varies across the life cycle remains poorly defined. Using full-len...
Evolution of the variant surface glycoprotein family in African trypanosomes
Silva Pereira, Sara; Jackson, Andrew P.; Figueiredo, Luisa M.An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-sp...
Immunopathology and Trypanosoma congolense parasite sequestration cause acute c...
De Niz, Mariana; Silva Pereira, Sara; Serre, Karine; Ouarné, Marie; Coelho, Joana E; Franco, Claudio; Figueiredo, Luisa M.Trypanosoma congolense causes a syndrome of variable severity in animals in Africa. Cerebral trypanosomiasis is a severe form, but the mechanism underlying this severity remains unknown. We developed a mouse model of acute cerebral trypanosomiasis and characterized the cellular, behavioral, and physiological consequences of this infection. We show large parasite sequestration in the brain vasculature for long p...
Surgical and intravital microscopy protocol to image Trypanosoma brucei–host in...
De Niz, Mariana; Figueiredo, Luisa M.Intravital microscopy (IVM) involves surgical procedures to expose the internal organs of live anesthetized animals to visualize fluorescently labeled components in situ, in vivo at subcellular resolution. Here, we provide an IVM protocol for time-lapse imaging of dynamic Trypanosoma brucei-host interactions in ten mammalian organs and in systemic circulation. We describe intraperitoneal or intradermal injectio...
Slow growing behavior in African trypanosomes during adipose tissue colonization
Trindade, Sandra; De Niz, Mariana; Sequeira, Mariana; Rebelo, Tiago; Bento, Fabio; Dejung, Mario; Narciso, Marta Valido; Escobar, Lara; Ferreira, JoãoWhen 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 prote...
A long noncoding RNA promotes parasite differentiation in African trypanosomes
Guegan, Fabien Marc; Rajan, K. Shanmugha; Bento, Fabio; Neves, Daniel; Sequeira, Mariana; Gumińska, Natalia; Mroczek, Seweryn; Dziembowski, AndrzejThe parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we ...
A novel lipase with dual localisation in Trypanosoma brucei
Monic, S. G.; Lamy, A.; Thonnus, M.; Bizarra-Rebelo, T.; Bringaud, F.; Smith, T. K.; Figueiredo, Luisa M.; Rivière, L.Phospholipases are esterases involved in lipid catabolism. In pathogenic micro-organisms (bacteria, fungi, parasites) they often play a critical role in virulence and pathogenicity. A few phospholipases (PL) have been characterised so far at the gene and protein level in unicellular parasites including African trypanosomes (AT). They could play a role in different processes such as host-pathogen interaction, an...
N6-methyladenosine in poly(A) tails stabilize VSG transcripts
Viegas, Idálio; Macedo, Juan; Serra, Lúcia; De Niz, Mariana; Temporão, Adriana; Silva Pereira, Sara; Mirza, Aashiq H.; Bergstrom, Ed; Rodrigues, Joao A.RNA modifications are important regulators of gene expression1. In Trypanosoma brucei, transcription is polycistronic and thus most regulation happens post-transcriptionally2. N6-methyladenosine (m6A) has been detected in this parasite, but its function remains unknown3. Here we found that m6A is enriched in 342 transcripts using RNA immunoprecipitation, with an enrichment in transcripts encoding variant surfac...
Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
Temporão, Adriana; Sanches-Vaz, Margarida; Luís, Rafael; Nunes-Cabaço, Helena; Smith, Terry K.; Prudêncio, Miguel; Figueiredo, Luisa M.Malaria, a disease caused by Plasmodium parasites, remains a major threat to public health globally. It is the most common disease in patients with sleeping sickness, another parasitic illness, caused by Trypanosoma brucei. We have previously shown that a T. brucei infection impairs a secondary P. berghei liver infection and decreases malaria severity in mice. However, whether this effect requires an active try...
Trypanosoma brucei triggers a broad immune response in the adipose tissue
Machado, Henrique; Rebelo, Tiago; Sequeira, Mariana; Trindade, Sandra; Carvalho, Tânia; Rijo-Ferreira, Filipa; Rentroia-Pacheco, Barbara; Serre, KarineAdipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome...