Unraveling Coronin in Plasmodium falciparum: A Key Player in Artemisinin Resistance?
As resistance to artemisinin-based therapies continues to threaten malaria control efforts, researchers have turned their attention to a suite of genes in Plasmodium falciparum that may play a role in drug tolerance. Among them, coronin is emerging as an intriguing candidate worth watching.
What Is Coronin?
Coronin is a conserved actin-binding protein found in many eukaryotic organisms, including parasites like Plasmodium falciparum. It regulates the parasite’s actin cytoskeleton, impacting critical processes such as:
Intracellular motility
Vesicle trafficking
Host-cell invasion
In P. falciparum, coronin helps maintain the structural integrity and dynamic remodeling of actin filaments—essential for the parasite’s survival and replication.
Coronin, Kelch13 and PI3K in Artemisinin Resistance?
Recent studies have observed mutations in the coronin gene (PF3D7_1251200) in laboratory-evolved artemisinin-resistant parasite lines, although such mutations are not yet widely seen in field isolates (Demas et al., 2018)
Possible Roles in Resistance:
Altered actin dynamics may affect the stress response pathways under artemisinin exposure.
Mutations in coronin may act synergistically with other resistance-associated genes, such as Kelch13.
How Does Coronin Compare to Kelch13 and PI3K?
Coronin is part of a larger molecular network possibly involved in resistance. Let’s briefly compare it with two other important players:
Kelch13 (K13): The Primary Genetic Marker
Gene: PF3D7_1343700
Role: K13 mutations (e.g., C580Y) are well-established markers for artemisinin resistance.
Function: Involved in stress response and protein regulation, possibly through protein degradation pathways.
Use in Surveillance: YES – routinely tracked globally (Mbengue et al., 2015).
PI3K (Phosphoinositide 3-Kinase): A Downstream Effector
Gene: PF3D7_0515300
Role: Not directly mutated in resistant parasites but becomes activated downstream of K13 mutations.
Function: Catalyzes lipid signaling involved in vesicle trafficking and membrane dynamics.
Connection: Increased PI3K activity and elevated PI3P levels are linked to K13-mediated resistance.
Comparison Table
Why It Matters
Understanding coronin's contribution to resistance may help refine our models of how artemisinin resistance evolves. Combined with confirmed markers like K13 and downstream players like PI3K, coronin could eventually:
Serve as a supporting biomarker
Highlight new targets for therapeutic intervention
Reveal evolutionary pathways of drug resistance
Conclusion
While coronin is still under investigation, it underscores the complexity of antimalarial resistance and the need to look beyond single-gene models. With molecular tools like CRISPR-Cas9 gene editing, scientists are poised to uncover whether coronin mutations cause, enhance, or compensate for artemisinin resistance.
Bibliography
Demas, A. R., Sharma, A. I., Wong, W., Early, A. M., Redmond, S., Bopp, S., Neafsey, D. E., Volkman, S. K., Hartl, D. L., & Wirth, D. F. (2018). Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. PNAS, 115(50), 12799–12804.
Mbengue, A., Bhattacharjee, S., Pandharkar, T., Liu, H., Estiu, G., Stahelin, R. V., Rizk, S., Njimoh, D. L., Ryan, Y., Chotivanich, K., Nguon, C., Ghorbal, M., Lopez- Rubio, J.-J., Pfrender, M., Emrich, S., Mohandas, N., Dondorp, A. M., Wiest, O., & Haldar, K. (2015). A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature, 520(7549), 683–687. https://doi.org/10.1038/nature14412
Batugedara, G., Lu, X. M., Hristov, B., Abel, S., Chahine, Z., Hollin, T., Williams, D., Wang, T., Cort, A., Lenz, T., Thompson, T. A., & Prudhomme, J. (2023). Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum. Nature Communications, 14, 5086.
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