Updated List of Transport Proteins in Plasmodium falciparum

Front Cell Infect Microbiol. 2022 Jun 24:12:926541. doi: 10.3389/fcimb.2022.926541. eCollection 2022.

Abstract

Malaria remains a leading cause of death and disease in many tropical and subtropical regions of the world. Due to the alarming spread of resistance to almost all available antimalarial drugs, novel therapeutic strategies are urgently needed. As the intracellular human malaria parasite Plasmodium falciparum depends entirely on the host to meet its nutrient requirements and the majority of its transmembrane transporters are essential and lack human orthologs, these have often been suggested as potential targets of novel antimalarial drugs. However, membrane proteins are less amenable to proteomic tools compared to soluble parasite proteins, and have thus not been characterised as well. While it had been proposed that P. falciparum had a lower number of transporters (2.5% of its predicted proteome) in comparison to most reference genomes, manual curation of information from various sources led to the identification of 197 known and putative transporter genes, representing almost 4% of all parasite genes, a proportion that is comparable to well-studied metazoan species. This transporter list presented here was compiled by collating data from several databases along with extensive literature searches, and includes parasite-encoded membrane-resident/associated channels, carriers, and pumps that are located within the parasite or exported to the host cell. It provides updated information on the substrates, subcellular localisation, class, predicted essentiality, and the presence or absence of human orthologs of P. falciparum transporters to quickly identify essential proteins without human orthologs for further functional characterisation and potential exploitation as novel drug targets.

Keywords: Plasmodium falciparum; calcium homeostasis; drug target; malaria; nutrient uptake; systems biology; transport pathway; transporters and channels.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials*
  • Humans
  • Ion Channels / metabolism
  • Malaria, Falciparum* / parasitology
  • Plasmodium falciparum / genetics
  • Proteomics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism

Substances

  • Antimalarials
  • Ion Channels
  • Protozoan Proteins