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.

Molecular evidence of a Trypanosoma brucei gambiense sylvatic cycle in the human african trypanosomiasis foci of Equatorial Guinea

“…Indeed, there is no apparent association between the rate of infection and taxonomic order in either T. b. brucei or T. b. gambiense , suggesting that these parasites can adapt to a wide range of species with no evident preference. This is consistent with previous findings that point out the ability of trypanosomes to proliferate in several species in both in vivo and in vitro experiments ( Bitter et al, 1998 ; Herder et al, 2002 ; Njiokou et al, 2006 ; Cordon-Obras et al, 2013 ). Besides, it is well known that most of the other human pathogenic kinetoplastids like T. b. rhodesiense, T. cruzi , or Leishmania sp.…”

Iron Homeostasis andTrypanosoma bruceiAssociated Immunopathogenicity Development: A Battle/Quest for Iron

“…Furthermore, the different copies of ESAG6/7 sequences are highly polymorphic in regions corresponding to Tf binding sites, whereby small changes in the amino acids present in the surface exposed-loops drastically affect the affinity of the receptor for a given Tf, thereby contributing to an additional mechanism of trypanosomes to acquire iron and to permit their rapid adaptation in distinct hosts [ 56 , 57 ]. Importantly, similar observations as for the T. b. brucei parasites with respect to the ESAG6/7 were observed for the T. b. rhodesiense and T. b. gambiense parasites [ 58 , 59 ]. This Tf-R polymorphism which allows selecting for high affinity Tf-Rs together with the rapid recycling of Tf-R and gene-specific activation events enables trypanosomes to efficiently compete for limiting substrate and withstand iron deprivation until a new set of Tf-R is expressed [ 55 , 60 , 61 ].…”

Localization of serum resistance-associated protein inTrypanosoma brucei rhodesienseand transgenicTrypanosoma brucei brucei

“…Cells were then fixed at least for one hour at 4 °C in 1% PFA diluted in cold PBS. Parasites were finally washed twice with PBS and labelled cells were analysed with a Becton Dickinson FACS Calibur TM flow cytometer (BD Biosciences) using BD CellQuest™ Pro version 4.0.2 software (Cordon-Obras et al , 2013).…”