Trypanosomes change their transferrin receptor expression to allow effective uptake of host transferrin

In its mammalian host, Trypanosoma brucei covers its iron requirements by receptor-mediated uptake of host transferrin (Tf). The Tf-receptor (Tf-R) is a heterodimeric membrane protein encoded by expression site-associated gene (ESAG) 6 and 7 located promoter-proximal in a polycistronic expression site (ES). Each of the 20 ESs encodes a slightly different Tf-R; these differences strongly affect the binding affinity for Tfs of different hosts. The Tf-R encoded in the 221 ES has a low affinity for dog Tf. Transfer of trypanosomes with an active 221 ES to dilute dog serum leads to growth arrest, which they can overcome by switching to another ES encoding a Tf-R with higher affinity for dog Tf. Here we show that trypanosomes can also adapt to dilute dog serum without switching but by replacing the ESAG7 gene in the 221 ES by one from another ES, by deleting ESAG7 from the 221 ES with concomitant upregulation of transcription of ESAG7 in 'silent' ESs, by grossly overproducing the 221 Tf-R or by combinations of these alterations. Our results illustrate the striking genetic flexibility of trypanosomes.