Analysis of a malaria sporozoite protein family required for gliding motility and cell invasion: Response

We were surprised to read such strong objections to the experimental strategy that we developed to investigate the functional significance of the amino acid residues shared by the thrombospondin-related adhesive proteins (TRAP) found in Plasmodium berghei (PbTRAP) and Plasmodium falciparum (PfTRAP)1. Not only have complementation experiments, using heterologous host systems, been widely used to elucidate gene function in a variety of organisms, but Drs Nussenzweig and Menard themselves have used such an approach to assess the function of conserved residues in the TRAP cytoplasmic tail: ‘cytoplasmic domains of this family (TRAP) are interchangeable indicating that they perform a similar function’2. What Drs Nussenzweig and Menard omit to say is that MIC2, the homologue of PbTRAP in Toxoplasma gondii, is less than 30% homologous to PbTRAP in the cytoplasmic tail. We wonder what makes it appropriate for them to use an experimental procedure that they regard as daring and unorthodox when used by us. As far as the vertebrate host range of P. berghei is concerned, we are aware that this parasite species does not infect humans. However, in vitro, P. berghei sporozoites are perfectly capable of invading human hepatocytes, where they can complete their development; this provided the rationale behind the study of P. falciparum molecules, that were implicated in the recognition and invasion process, in P. berghei.