Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes
Issued Date
2026-01-01
Resource Type
ISSN
00064971
eISSN
15280020
Scopus ID
2-s2.0-105034510617
Pubmed ID
41701978
Journal Title
Blood
Rights Holder(s)
SCOPUS
Bibliographic Citation
Blood (2026)
Suggested Citation
Zinga M., Ibrahim A., Mohring F., Chainarin S., Jonsdottir T.K., Ngernna S., Amabilino-Perez B., Pholcharee T., Turkiewicz A., Campino S., Clark T.G., Miao J., Cui L., Roobsoong W., Sattabongkot J., Moon R.W., Nguitragool W. Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes. Blood (2026). doi:10.1182/blood.2025029557 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116044
Title
Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes
Corresponding Author(s)
Other Contributor(s)
Abstract
Plasmodium knowlesi, a zoonotic malaria species, has become a significant public health concern in Southeast Asia. In regions such as Malaysia and southern Thailand, P knowlesi incidence has risen, even as other human malaria parasites are nearing elimination. Similar to its close relative Plasmodium vivax, P knowlesi relies on the Duffy antigen receptor for chemokine (DARC) as a key receptor for erythrocyte invasion. Only Duffy-positive individuals are thought to be susceptible to clinical infection. Here, we demonstrate that P knowlesi possesses greater invasion plasticity than previously recognized. This parasite can bypass the need for DARC, as shown by its in vitro adaptation to invade and replicate within Duffy-negative (Fy−) erythrocytes. This adaptation is stable and independent of DARC binding, enabling the adapted parasite line to be maintained in Fy− erythrocytes and to resist inhibition by α-DARC antibodies. Genomic analysis identified a genomic recombination event between the parasite's dbp<inf>α</inf> and dbp<inf>γ</inf> genes, resulting in a new chimeric gene dbp<inf>αγ</inf>. Using CRISPR-Cas9 targeted reversion, we could demonstrate that dbp<inf>αγ</inf> is essential for invasion of Fy− erythrocytes. These findings shed new light on the invasion plasticity of P knowlesi, with implications for the parasite’s potential spread beyond Southeast Asia and for understanding the complex host-cell specificity and atypical invasion pathways seen in P vivax.