Release of merozoites from Plasmodium falciparum -infected erythrocytes could be mediated by a non-explosive event

Winograd, Enrique; Clavijo, Carlos; Bustamante, Leyla Y.; Jaramillo, Martiza

doi:10.1007/s004360050606

Cited by 31 publications

(19 citation statements)

References 12 publications

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“…Vapor bubbles can also be generated via optical absorbance of hemoglobin in uninfected RBCs but at more than 100-fold higher laser fluence (35). We believe that the H-VNB method may similarly detect free hemozoin in the residual bodies after merozoite release or in tissue (36). Although such hemozoin does not contribute to the standard parasitemia count, its presence is associated with malaria infection (37,38), and therefore, its detection also has diagnostic value.…”

Section: Discussionmentioning

confidence: 99%

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Lukianova‐Hleb¹,

Campbell

Constantinou³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Successful diagnosis, screening, and elimination of malaria critically depend on rapid and sensitive detection of this dangerous infection, preferably transdermally and without sophisticated reagents or blood drawing. Such diagnostic methods are not currently available.Here we show that the high optical absorbance and nanosize of endogenous heme nanoparticles called "hemozoin," a unique component of all blood-stage malaria parasites, generates a transient vapor nanobubble around hemozoin in response to a short and safe near-infrared picosecond laser pulse. The acoustic signals of these malaria-specific nanobubbles provided transdermal noninvasive and rapid detection of a malaria infection as low as 0.00034% in animals without using any reagents or drawing blood. These on-demand transient events have no analogs among current malaria markers and probes, can detect and screen malaria in seconds, and can be realized as a compact, easy-to-use, inexpensive, and safe field technology.

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Section: Discussionmentioning

confidence: 99%

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Lukianova‐Hleb¹,

Campbell

Constantinou³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Video microscopy studies (Winograd et al 1999) have shown that merozoites exit the infected erythrocyte together with the residual body containing haemozoin, leaving behind a structurally stable infected erythrocyte``ghost''. Since the haemoglobin-rich cytoplasm of the infected erythrocyte does not diuse out as parasites are being released, it appears that merozoite release is not the result of an explosive event.…”

Section: Introductionmentioning

confidence: 99%

Cytoadherence of the malaria-infected erythrocyte membrane to C32 melanoma cells after merozoites are released from parasitized infected cells

Winograd¹,

Robles²,

Caldas

et al. 2001

Parasitol Res

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Infections with the human malaria parasite Plasmodium falciparum are characterized by cytoadherence of infected erythrocytes to the venular endothelium of several organs. Video microscopy studies have shown that at the end of the asexual life of P. falciparum, the residual body containing haemozoin is released to the extracellular environment along with merozoites, leaving behind an infected erythrocyte "ghost". It is possible that these infected erythrocyte "ghosts" could remain sequestered within the blood vessels of patients infected with P. falciparum even after merozoites have been released from infected erythrocytes. In this study an in vitro cytoadherence assay was developed to show that infected erythrocyte "ghosts" can interact with C32 melanoma cells. Adherent infected erythrocyte "ghosts" contain some of the subcellular compartments of the malaria-infected red blood cell such as the tubo-vesicular membrane network and remnants of the parasitophorous vacuolar membrane, but lack haemozoin.

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“…By using a combination of E64, a cysteine protease inhibitor, and a specific antibody labeling approach, Salmon et al (6) proposed a twostep process for parasite release that includes an initial exit of merozoites enclosed within the PVM followed by a rapid parasite escape by a proteolysis-dependent mechanism. Secondly, Winograd et al (7) used video microscopy to study the release of merozoites and concluded that an aperture is made through the PVM as well as the red cell membrane to allow merozoite exit in an orderly fashion. Another report from the same group (8) detected fragments of erythrocyte membrane and PVM in culture medium at the time of merozoite release from infected RBCs.…”

Section: (1) After Invasion Intomentioning

confidence: 99%

Ankyrin Peptide Blocks Falcipain-2-mediated Malaria Parasite Release from Red Blood Cells

Dhawan

Dua

Chishti

et al. 2003

Journal of Biological Chemistry

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Falcipain-2 (FP-2) is a dual-function protease that cleaves hemoglobin at the early trophozoite stage and erythrocyte membrane ankyrin and protein 4.1 at the late stages of parasite development. FP-2-mediated cleavage of ankyrin and protein 4.1 is postulated to cause membrane instability facilitating parasite release in vivo. To test this hypothesis, here we have determined the precise peptide sequence at the hydrolysis site of ankyrin to develop specific inhibitor(s) of FP-2. Mass spectrometric analysis of the hydrolysis products showed that FP-2-mediated cleavage of ankyrin occurred immediately after arginine 1,210. A 10-mer peptide (ankyrin peptide, AnkP) containing the cleavage site completely inhibited the FP-2 enzyme activity in vitro and abolished all of the known functions of FP-2. To determine the effect of this peptide on the growth and development of P. falciparum, the peptide was delivered into intact parasite-infected red blood cells (RBCs) via the Antennapedia homeoprotein internalization domain. Growth and maturation of trophozoites and schizonts was markedly inhibited in the presence of the fused AnkP peptide. <10% of new ring-stage parasites were detected compared with the control sample. Together, our results identify a specific peptide derived from the spectrin-binding domain of ankyrin that blocks late-stage malaria parasite development in RBCs. Confocal microscopy with FP-2-specific antibodies demonstrated the proximity of the enzyme in apposition with the RBC membrane, further corroborating the proposed function of FP-2 in the cleavage of RBC skeletal proteins.Plasmodium falciparum causes the most severe form of human malaria and is responsible for nearly all malaria-induced mortality. Clinical manifestations of malaria are caused by the intraerythrocytic life cycle of P. falciparum. The parasite undergoes distinct morphologic changes during its 48-h life cycle inside human red blood cells (RBCs) 1 (1). After invasion into RBCs, the parasites mature from ring stage to trophozoites and then to schizonts. Mature segmented schizonts finally rupture the host erythrocytes releasing merozoites, which rapidly invade other erythrocytes to reinitiate the cycle. The mechanism of merozoite release from host RBCs is largely unknown. The cluster of merozoites inside a red blood cell is enclosed within two membranes: an inner parasitophorous vacuole membrane (PVM) and an outer RBC membrane. The rupture of these two membranes precedes the release of merozoites for subsequent round of RBC invasion. Several studies have shown that the merozoite release is susceptible to protease inhibitors. In the presence of such inhibitors, merozoites mature normally but are unable to escape from RBCs (2-4). Furthermore, a number of plasmodial proteases have been isolated and are shown to have activities against known RBC membrane skeletal proteins (5), although a functional role of these proteases in the rupture of the RBC membrane during merozoite escape has not been established.The issue of malaria parasite release fro...

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Release of merozoites from Plasmodium falciparum -infected erythrocytes could be mediated by a non-explosive event

Cited by 31 publications

References 12 publications

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Cytoadherence of the malaria-infected erythrocyte membrane to C32 melanoma cells after merozoites are released from parasitized infected cells

Ankyrin Peptide Blocks Falcipain-2-mediated Malaria Parasite Release from Red Blood Cells

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