The <i>Plasmodium</i> PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites

<div><p>The <i>phist</i> gene family has members identified across the <i>Plasmodium</i> genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in <i>P</i>. <i>falciparum</i>, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite <i>P</i>. <i>berghei</i> 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the <i>P</i>. <i>berghei phist</i> genes are predominant in schizonts, whereas in <i>P</i>. <i>falciparum</i> transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of <i>P</i>. <i>berghei phist</i> genes in order to characterize a simplistic model for the expanded <i>phist</i> gene repertoire in <i>P</i>. <i>falciparum</i>. Unsuccessful attempts to disrupt <i>P</i>. <i>berghei PBANKA_114540</i> suggest that this <i>phist</i> gene is essential, while knockout of <i>phist PBANKA_122900</i> shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>berghei phist</i> genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three <i>P</i>. <i>berghei</i> PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites.</p>