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

Saini, E., Sheokand, P. K., Sharma, V., Agrawal, P., Kaur, I., Singh, S., Mohmmed, A. and Malhotra, P. (2021) Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes. PLoS Pathogens, 17(7), e1009750. (doi: 10.1371/journal.ppat.1009750) (PMID:34324609) (PMCID:PMC8321122)

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.

• Item Type: Articles
• Additional Information: 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).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sheokand, Mr Pradeep Kumar

Creator Roles

Sheokand, P. K.: Data curation, Investigation, Methodology, Resources, Validation

• Authors: Saini, E., Sheokand, P. K., Sharma, V., Agrawal, P., Kaur, I., Singh, S., Mohmmed, A., and Malhotra, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 29 July 2021
• Copyright Holders: Copyright © 2021 Saini et al.
• First Published: First published in PLoS Pathogens 17(7): e1009750
• Publisher Policy: Reproduced under a Creative Commons License