Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes

PLoS Pathog. 2021 Jul 29;17(7):e1009750. doi: 10.1371/journal.ppat.1009750. eCollection 2021 Jul.

Abstract

The human malaria parasite, Plasmodium falciparum possesses unique gliding machinery referred to as the glideosome that powers its entry into the insect and vertebrate hosts. Several parasite proteins including Photosensitized INA-labelled protein 1 (PhIL1) have been shown to associate with glideosome machinery. Here we describe a novel PhIL1 associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of the merozoite. Using an experimental genetics approach, we characterized the role(s) of three proteins associated with PhIL1: a glideosome associated protein- PfGAPM2, an IMC structural protein- PfALV5, and an uncharacterized protein-referred here as PfPhIP (PhIL1 Interacting Protein). Parasites lacking PfPhIP or PfGAPM2 were unable to invade host RBCs. Additionally, the downregulation of PfPhIP resulted in significant defects in merozoite segmentation. Furthermore, the PfPhIP and PfGAPM2 depleted parasites showed abrogation of reorientation/gliding. However, initial attachment with host RBCs was not affected in these parasites. Together, the data presented here show that proteins of the PhIL1-associated complex play an important role in the orientation of P. falciparum merozoites following initial attachment, which is crucial for the formation of a tight junction and hence invasion of host erythrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythrocytes / parasitology*
  • Humans
  • Malaria, Falciparum / metabolism*
  • Malaria, Falciparum / parasitology*
  • Merozoites / metabolism*
  • Protozoan Proteins / metabolism*

Substances

  • Protozoan Proteins

Grants and funding

ES acknowledges the financial support from the Department of Biotechnology, Government of India in the form of a DBT-JRF Fellowship. PKS and VS are awardees of a fellowship from the University Grants Commission (UGC) and Council of Scientific & Industrial Research (CSIR), Govt. of India, respectively. The research work in PM's and AM’s laboratory is supported by Flagship Project (BT/IC-06/003/91), and Centre of Excellence grant (BT/COE/34/SP15138/2015) from the Department of Biotechnology, Govt. of India. PM is a recipient of the J C Bose Fellowship awarded by SERB, Govt. of India, and work is supported by the grant (DST/20/015). The funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.