Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach

Area of Science:

• Malariology
• Parasitology
• Molecular Biology

Background:

• Malaria symptoms arise from blood-stage parasites invading human erythrocytes.
• Understanding erythrocyte invasion is crucial but limited by the short invasive period of merozoites.

Purpose of the Study:

• To investigate the molecular basis for enhanced erythrocyte invasion by a Plasmodium falciparum long-lived merozoite (LLM) line.
• To identify key proteins and pathways involved in Plasmodium falciparum merozoite invasion.

Main Methods:

• Development of a gamma-irradiated long-lived merozoite (LLM) line of Plasmodium falciparum.
• Integrated omics approach, including genomics, transcriptomics, and label-free quantitative mass-spectrometry.
• Characterization of merozoite surface protein complex and protein abundance profiling.

Main Results:

• LLMs exhibited a 10-300 fold increase in erythrocyte invasion compared to wild-type (WT) merozoites.
• Genomic and transcriptomic analyses revealed minimal differences; however, proteomic analysis showed significant changes in protein abundance.
• Over 1100 proteins were quantified, with 200 proteins of unknown function identified. A unique processed MSP1 intermediate was observed in LLMs.

Conclusions:

• The merozoite proteome plays a significant role in Plasmodium falciparum erythrocyte invasion.
• The study identified numerous unknown proteins potentially involved in invasion, offering new targets for antimalarial strategies.
• Delayed processing of major merozoite surface protein 1 (MSP1) may contribute to the enhanced invasion phenotype.