Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi.
The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; Rob.Moon@lshtm.ac.uk Tony.Holder@crick.ac.uk.
Robert W
RW
Moon
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia;
Hazem
H
Sharaf
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom;
Claire H
CH
Hastings
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia;
Yung Shwen
YS
Ho
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia;
Mridul B
MB
Nair
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia;
Zineb
Z
Rchiad
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom;
Ellen
E
Knuepfer
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia;
Abhinay
0000-0001-9372-5526
A
Ramaprasad
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
Franziska
F
Mohring
Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
Amirah
A
Amir
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom; Parasitology Unit, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia;
Noor A
NA
Yusuf
Division of Retrovirology, National Institute for Biological Standards and Control, Health Protection Agency, Hertfordshire EN6 3QG, United Kingdom;
Joanna
J
Hall
Division of Retrovirology, National Institute for Biological Standards and Control, Health Protection Agency, Hertfordshire EN6 3QG, United Kingdom;
Neil
N
Almond
Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
Yee Ling
YL
Lau
Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah 23955-6900, Kingdom of Saudi Arabia; Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan;
Arnab
A
Pain
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom; Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
Michael J
MJ
Blackman
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom; Rob.Moon@lshtm.ac.uk Tony.Holder@crick.ac.uk.
Anthony A
0000-0002-8490-6058
AA
Holder
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008288:Malaria; D016790:Plasmodium knowlesi / Q000235:genetics* / Q000472:pathogenicity*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D015047:Zoonoses
D002352:Carrier Proteins; D015800:Protozoan Proteins
Plasmodium knowlesi; invasion; malaria parasite; normocyte-binding protein; zoonotic malaria