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Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes

Tiffany M DeSimone1, Cameron V Jennings, Amy K Bei

  • 1Harvard School of Public Health, Boston, MA 02115, USA.

Molecular Microbiology
|April 30, 2009
PubMed

Insights

Plasmodium falciparum invasion relies on erythrocyte receptors. This study shows PfRh2a and PfRh2b ligands are crucial for efficient sialic acid-independent invasion, with PfRh2b expression favored.

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Cellular Biology

Background:

  • Plasmodium falciparum causes severe malaria and exhibits variable dependence on host erythrocyte receptors for invasion.
  • Reticulocyte-binding protein-like (RBL) proteins are key invasion ligands influencing parasite pathways.
  • Understanding these ligands is critical for developing malaria control strategies.

Purpose of the Study:

  • To investigate the roles of PfRh2a and PfRh2b invasion ligands in P. falciparum erythrocyte invasion.
  • To determine the functional significance of these ligands in a strain dependent on sialic acid receptors.
  • To explore the impact of genetic background on ligand-receptor interactions.

Main Methods:

  • Targeted gene disruption of PfRh2a and PfRh2b in the W2mef P. falciparum strain.
  • Analysis of parasite invasion efficiency using sialic acid-depleted erythrocytes.
  • Assessment of selective pressure for gene expression in disrupted parasite lines.

Main Results:

  • PfRh2b is functional in the W2mef strain, which relies on sialic acid receptors.
  • Parasites lacking PfRh2a or PfRh2b can switch to sialic acid-independent invasion.
  • Both ligands contribute to efficient sialic acid-independent invasion, with a preference for PfRh2b re-expression.

Conclusions:

  • Genetic background significantly influences P. falciparum ligand-receptor usage.
  • PfRh2a and PfRh2b coordinate to mediate efficient sialic acid-independent erythrocyte invasion.
  • Targeting these invasion pathways could offer new avenues for malaria intervention.

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