Polymorphism in a Plasmodium falciparum erythrocyte-binding ligand changes its receptor specificity

Area of Science:

• Malariology
• Parasitology
• Molecular Biology

Background:

• Plasmodium falciparum uses erythrocyte binding-like (EBL) proteins, including BA erythrocyte binding ligand (BAEBL), to invade human erythrocytes.
• Previous studies indicated variations in BAEBL binding specificity across different parasite clones.

Purpose of the Study:

• To investigate the sequence and erythrocyte binding specificity of Region II of BAEBL in P. falciparum clones globally.
• To understand how BAEBL polymorphisms contribute to invasion pathway diversity.

Main Methods:

• Sequencing of Region II of BAEBL from various P. falciparum clones.
• Expression of BAEBL polymorphisms on COS cells and binding assays with enzyme-treated and Gerbich-negative erythrocytes.
• Erythrocyte-binding assays using native, radiolabeled BAEBL from culture supernatant.

Main Results:

• Five nucleotide substitutions and five amino acid polymorphisms were identified in Region II of BAEBL.
• Four expressed BAEBL polymorphisms demonstrated distinct binding specificities to different erythrocyte receptors.
• Both in vitro expression assays and native protein assays confirmed differential receptor binding.

Conclusions:

• Polymorphisms in the P. falciparum BAEBL ligand are associated with distinct erythrocyte receptor binding.
• These findings suggest that P. falciparum has evolved multiple invasion pathways driven by BAEBL ligand variations.