Abstract
The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts. In this study, we analyzed SBP1 orthologs across the Plasmodium genus by BLAST analysis and conserved gene synteny, which were also recently described by de Niz et al. (2016). To evaluate the localization of an SBP1 ortholog, we utilized the zoonotic malaria parasite, Plasmodium knowlesi. Immunofluorescence assay of transgenic P. knowlesi parasites expressing epitope-tagged recombinant PkSBP1 revealed a punctate staining pattern reminiscent of Maurer's clefts, following infection of either monkey or human erythrocytes. The recombinant PkSBP1-positive puncta co-localized with Giemsa-stained structures, known as ‘Sinton and Mulligan’ stipplings. Immunoelectron microscopy also showed that recombinant PkSBP1 localizes within or on the membranous structures akin to the Maurer's clefts. The recombinant PkSBP1 expressed in P. falciparum-infected erythrocytes co-localized with PfSBP1 at the Maurer's clefts, indicating an analogous trafficking pattern. A member of the P. knowlesi 2TM protein family was also expressed and localized to membranous structures in infected monkey erythrocytes. These results suggest that the trafficking machinery and induced erythrocyte cellular structures of P. knowlesi are similar following infection of both monkey and human erythrocytes, and are conserved with P. falciparum.
Highlights
Despite a 37% decrease in the global incidence of malaria due to interventions in the past 15 years, the malaria parasite has consistently innovated ways to thwart control efforts
A candidate SBP1 protein for P. knowlesi was identified by BLASTP analysis using the P. falciparum SBP1 amino acid sequence as a query of GenBank and the Plasmodium genome databases accessed at PlasmoDB independently from the recent report by de Niz et al (2016) [28]
SBP1 proteins share a general protein structure highlighted by the absence of a signal peptide sequence and Plasmodium Export Element (PEXEL) or host targeting (HT) erythrocyte targeting motif [30,31], the presence of a central low complexity or repeat region (Fig 1B), and amino acid sequence similarity confined to a region adjacent to the single transmembrane region (Fig 1C)
Summary
Despite a 37% decrease in the global incidence of malaria due to interventions in the past 15 years, the malaria parasite has consistently innovated ways to thwart control efforts. Control efforts largely focus on the virulent Plasmodium falciparum, and the widespread Plasmodium vivax, with lesser emphasis targeting other Plasmodium species that cause human malaria. P. knowlesi is traditionally considered a non-human malaria parasite, found in Southeast Asia infecting macaque monkeys, and humans as a zoonotic infection [4]. For such zoonotic parasites, increased direct or close contact with humans and animals results from urbanization, and for P. knowlesi represents another obstacle in the general fight against malaria. Human-animal contact is pivotal in expanding host niches potentiating the adaptation of simian Plasmodium species to human hosts [5,6]
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