Authors

M Zinga²; A Ibrahim¹; F Mohring¹; S Chainarin²; TK Jonsdottir¹; S Ngernna²; B Amabilino-Perez³; T Pholcharee³; A Turkiewicz¹; S Campino¹; T Clark¹; J Miao⁴; L Cui⁴; W Roobsoong²; J Sattabongkot²; R Moon¹; W Nguitragool²;  ¹ London School of Hygiene and Tropical Medicine, UK;  ² Mahidol - Oxford Tropical Medicine Research Unit, Thailand;  ³ Oxford University, UK;  ⁴ University of South Florida, United States

Discussion

Plasmodium knowlesi, a zoonotic malaria species, has become a significant public health concern in Southeast Asia. Despite progress in eliminating other human malaria parasites in Malaysia and southern Thailand, P. knowlesi cases have surged. Like Plasmodium vivax, P. knowlesi relies on Duffy-Antigen Receptor for Chemokines (DARC) in invading human erythrocytes and is thought to affect only Duffy-positive individuals. However, our current research demonstrates P. knowlesi's surprising invasion adaptability. We found that this parasite can overcome its dependence on DARC, adapting in lab conditions to invade and replicate within Duffy-negative (Fy-) erythrocytes. This adaptation, unrelated to DARC binding, remains stable and unaffected by α-DARC antibodies. Genomic analysis revealed a recombination between the parasite's similar genes, dbpα and dbpγ, creating a new chimeric gene. Through targeted genetic reversal, we confirmed its necessity for invading Duffy-negative erythrocytes. This discovery sheds light on P. knowlesi's invasion plasticity, vital for understanding its potential transmission beyond Southeast Asia and the intricate host cell tropism of P. vivax. This insight into atypical invasion pathways holds significance for malaria research and potential future interventions.