Year: 2026
Type: article
Abstract: 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 dbpα and dbpγ genes, resulting in a new chimeric gene dbpαγ. Using CRISPR-Cas9 targeted reversion, we could demonstrate that dbpαγ 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.
Source: Blood
Authors: Maria Zinga, Amy Ibrahim, Franziska Mohring, Sittinont Chainarin, Thorey K. Jonsdottir, Sutharinee Ngernna, Brian Amabilino-Perez, Tossapol Pholcharee, Anna Turkiewicz, Susana Campino, Taane G. Clark, Jun Miao, Liwang Cui, Wanlapa Roobsoong, Jetsumon Sattabongkot, Robert W. Moon, Wang Nguitragool
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
Funders: London School of Hygiene and Tropical Medicine, Wellcome Trust, UK Research and Innovation, Mahidol University, Organization for Women in Science for the Developing World, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Faculty of Tropical Medicine, Mahidol University
Awards: G1131867873, AI assisted genomic profiling for the personalisation of treatment and control of infections, Molecular dissection of the host-parasite interactions underlying malaria parasite erythrocyte invasion, Dissecting the Red Blood Cell Invasion Pathways of the Malaria Parasite Plasmodium knowlesi, G6529466185, Infection-AID: AI assisted genomic profiling to inform the Diagnosis, personalised treatment and control of infections, Molecular dissection of the host-parasite interactions underlying malaria parasite erythrocyte invasion, G7406135213, G7455513328, Elucidating the mechanism of reticulocyte-specific invasion by Plasmodium vivax., GenES_VBD network (Genomic Epidemiology tools for the Surveillance of Vector Borne Diseases: applied to tick species, reservoirs, and pathogens, G9000242701
OpenAlex ID: W7129565154