Protective Properties and Surface Localization ofPlasmodium falciparumEnolase

Abstract

The enolase protein of the human malarial parasite Plasmodium falciparum has recently been characterized. Apart from its glycolytic function, enolase has also been shown to possess antigenic properties and to be present on the cell wall of certain invasive organisms, such as Candida albicans. In order to assess whether enolase of P. falciparum is also antigenic, sera from residents of a region of Eastern India where malaria is endemic were tested against the recombinant P. falciparum enolase (r-Pfen) protein. About 96% of immune adult sera samples reacted with r-Pfen over and above the seronegative controls. Rabbit anti-r-Pfen antibodies inhibited the growth of in vitro cultures of P. falciparum. Mice immunized with r-Pfen showed protection against a challenge with the 17XL lethal strain of the mouse malarial parasite Plasmodium yoelii. The antibodies raised against r-Pfen were specific for Plasmodium and did not react to the host tissues. Immunofluorescence as well as electron microscopic examinations revealed localization of the enolase protein on the merozoite cell surface. These observations establish malaria enolase to be a potential protective antigen.Malaria continues to be a life-threatening infectious disease in the tropical world. Despite tremendous efforts to control the malaria epidemic, current prophylaxis and drug treatments are proving insufficient. The extensive spreading of drug-resistant Plasmodium strains as well as insecticide-resistant mosquitoes makes it urgent to develop an effective malaria vaccine. Long years of antigen identification and characterization have yielded many potential vaccine candidates, but developing an effective malaria vaccine has remained an incredibly difficult challenge (17). It has been observed that immunity to the disease develops gradually, after many attacks and over many years, in adults living in areas where malaria is endemic (2). The successful passive transfer of this immunity by injecting antibodies from malaria-immune persons to children susceptible to malaria has demonstrated that antibodies alone can trigger protection (5, 9, 58). These experiments have worked across geographical borders, as immunoglobulin G (IgG) from malaria-immune West Africans have cured East Africans as well as Thai malaria patients (5). The nature of this immunity is poorly understood at the molecular level. However, attempts have been made to identify antigens, the humoral response against which leads to protection. Seroepidemiological studies have identified several specific malarial blood-stage antigens including ring-infected erythrocyte surface antigen (10), apical membrane antigen (53), and PfP0, a conserved ribosomal protein (7,18,24), as protective antigens.Enolase has been reported to be present on the cell surface of several organisms (38). It is also considered to be a major immunostimulatory protein in the case of visceral leishmaniasis (19). Enolase has been demonstrated to play a protective role in Candida albicans infection (31, 41, 55). Recently, it has also been ...

Quantitative Proteomics Reveals New Insights into Erythrocyte Invasion by Plasmodium falciparum

“…One of these, enolase, is of interest because it has recently been shown to be expressed at the surface of the merozoite and has been implicated similar to aldolase to perform some "moonlighting" function during invasion (26,27). In W2mef, there also appears to be increased expression of proteins that are exported to the cytosol from the infected erythrocyte (Table II).…”

Elevated enolase and caveolin-1 in the heart of rats following dexamethasone-induced toxicity

“…Also it has been demonstrated that enolase is an essential protein in fungal metabolism (27), and its lack of expression may cause delays in larval development (28). Apart from its glycolytic function, enolase has also been shown to possess antigenic properties and to be present on the cell wall of certain invasive organisms, such as Candida albicans (29). In addition, it has been found that enolase levels are highly elevated in malaria parasite-infected red blood cells (30).…”

A glimpse into the clinical proteome of human malaria parasites Plasmodium falciparum and Plasmodium vivax

“…L-LDH, which is a possible drug target in malaria, was also found in the clinical ring stages [21,22]. Parasite enolase, which is thought to be exported to the infected erythrocyte surface [23], was also expressed in the clinical ring stages. Many other metabolic enzymes are detected in the ring-stage clinical isolates.…”