Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells

Abstract

Plasmodium falciparum causes the most lethal form of malaria in humans and is responsible for over two million deaths per year. The development of a vaccine against this parasite is an urgent priority and potential protein targets include those on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to transfect P. falciparum has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. In this review, we describe the use of this technology to examine the role of merozoite antigens in erythrocyte invasion and to address their potential as vaccine candidates.

Polymorphisms in Erythrocyte Binding Antigens 140 and 181 Affect Function and Binding but Not Receptor Specificity in Plasmodium falciparum

“…GYP A is one of the most abundant proteins on the red blood cell, and it is not surprising that invasion through this receptor, via EBA-175, would be more important than, for example, GYP C, which is present at lower levels (21). Further support for a less significant role for EBA-140 and EBA-181 in merozoite invasion, in comparison to EBA-175, is the ability to disrupt the corresponding genes in most parasites so far attempted (13,14). In contrast, it does not seem to be possible to disrupt the EBA-175 gene in D10, in which the available invasion pathways appear to be limited (13).…”

Low Multiplication Rates of African Plasmodium Falciparum Isolates and Lack of Association of Multiplication Rate and Red Blood Cell Selectivity With Malaria Virulence

“…[31][32][33][34] Our data are consistent with P. falciparum having the ability to down-regulate its multiplication rate to avoid overwhelming the host. We are not aware of any other experimental evidence to support such an idea; however, it is plausible that switching of invasion pathways [35][36][37][38][39] could potentially underlie such a process. It would be of great interest to examine the relationship between particular invasion pathways and parasite PMR and SI, and to determine whether the PMR and SI are stable properties of each isolate or can vary in response to external stimuli.…”

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

“…SERA2, -3, -7, and -8 were all disrupted by single crossover recombination technology. This process relies on the gene targeting event having little or no effect on blood stage growth, since the methodology depends on parasites possessing integrated forms of the plasmid outgrowing those containing episomally replicating forms (30,42,43,45). Hence, SERA2, -3, -7, and -8 are all either not involved, or play a redundant role, in the erythrocytic cycle.…”