title: Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.
abstract: Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs) by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs) we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES). Thus, Expression Site Associated Genes (ESAGs) sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR), expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf) uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection supporting previous epidemiological results.
authors.affiliation: Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Obras
authors.affiliation: Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cano
authors.affiliation: Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: González-Pacanowska
authors.affiliation: Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Benito
authors.affiliation: Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, Consejo Superior de Investigaciones Científicas, Granada, Spain ; Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Bart
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004197:Disease Reservoirs / Q000469:parasitology*; D005455:Fluorescent Antibody Technique; D014644:Genetic Variation; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006041:Goats; D006801:Humans; D008322:Mammals / Q000097:blood / Q000469:parasitology*; D008562:Membrane Glycoproteins / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000469:parasitology*; D013045:Species Specificity; D013552:Swine; D014168:Transferrin / Q000378:metabolism; D014347:Trypanosoma brucei gambiense / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D014168:Transferrin; C078011:ESAG 7 protein, Trypanosoma brucei