Discussion

The proliferative slender bloodstream form of Trypanosoma brucei stochastically switches the expressed variant surface glycoprotein (VSG) and, thus, escapes the immune attack of its mammalian host (antigenic variation). While parasitemia rises, the trypanosome-secreted stumpy induction factor (SIF) accumulates and upon reaching a threshold the slender cells differentiate to the G1/0 arrested fly-infective stumpy stage. Previously, we have shown that overexpression of an ectopic VSG leads to the attenuation of the entire active VSG expression site (ES), followed by growth retardation. This was reminiscent of stumpy stage formation and, thus, indicated that ES-attenuation could act as a trigger for stumpy development. We now have tested this possibility by VSG overexpression in a pleomorphic strain, which possesses full developmental competence. This revealed a marked phenotypic plasticity. Upon VSG overexpression the endogenous VSG was silenced in all clones, but surprisingly, the entire ES was not equally attenuated. We show that if the transcriptional activity of the ES falls below a specific threshold, the almost immediate development of fly-infective stumpy cells is induced. Our results also indicate that ES-attenuation triggers stumpy differentiation in a cell density-independent manner, downstream of the quorum sensing factor SIF. We suggest that the activity status of the ES represents the interface between antigenic variation and transmissibility.