MRC National Institute for Medical Research, London
Science for Health
Erythrocyte invasion by malaria parasites
23 February 2011
NIMR scientists have demonstrated parasite ligand plasticity for binding to receptors on the surface of the host red blood cell in a step that is integral to cell invasion. The research is published in PLoS Pathogens.
Malaria parasites invade host erythrocytes where they develop and multiply, causing the disease. Invasion is a complex process involving interactions between the surfaces of parasite and host cell, excretion of proteins from internal compartments of the parasite leading to the formation of a tight junction between the two cells, and movement of the parasite driven by its actomyosin motor into a vacuole created within the red blood cell. It has been known for some time that the pathways of invasion are redundant: for example experimental manipulation of the host cell surface by enzyme treatment can result in selection of a parasite population that uses one preferred pathway over another. Two parasite gene families have been shown to code for proteins that are key ligands in this process and there is evidence that the expression of some of these genes is under epigenetic control.
Sola Ogun (pictured) in Tony Holder’s lab in NIMR’s Division of Parasitology, together with collaborators at the University of Nottingham and the Wellcome Trust Sanger Institute, has shown that an alternative mechanism can also be employed by the parasite. In a rodent parasite, Plasmodium yoelii, all the genes in one family are expressed. Knocking out the gene for the primary ligand binding to erythrocytes has no effect on the level of transcription of other members of the family or other genes as judged by RNA-Seq global transcription analysis. Instead, a second protein of the family takes over as the invasion ligand, without apparent change in level of transcript or protein. This suggests that there is a molecular/functional hierarchy that determines which of the expressed ligands are used and is consistent with the ‘limited space’ hypothesis whereby the position of a particular ligand at the apex of the parasite determines the ligand used for invasion.
This study indicates that this malaria parasite can use a panel of redundant ligands to bind to the surface of the host red blood cell. This will enable it to recognise and invade a wide range of erythrocytes and potentially avoid blocking antibodies to any single ligand-receptor interaction. This plasticity is expressed in the absence of differences in gene expression.
Tony Holder
Original article
Solabomi A Ogun, Rita Tewari, Thomas D Otto, Steven A Howell, Ellen Knuepfer, Deirdre A Cunningham, Zhengyao Xu, Arnab Pain & Anthony A Holder (2011)
Targeted Disruption of py235ebp-1: Invasion of Erythrocytes by Plasmodium yoelii Using an Alternative Py235 Erythrocyte Binding Protein
PLoS Pathogens 7(2): e1001288. Full text.
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