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Category: Microbial Genetics and Molecular Biology
8 A Mechanistic Approach to Merozoite Invasion of Red Blood Cells: Merozoite Biogenesis, Rupture, and Invasion of Erythrocytes, Page 1 of 2
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This chapter provides an overview of the dynamic nature of malaria from the perspective of the development of merozoites within an infected erythrocyte and the release of infectious merozoites, through the initiation and completion of the reinvasion process. The chapter encompasses discoveries or observations obtained through studies of different species of Plasmodium, which together have greatly aided and refined our understanding of these events. These species include not only the human malarias Plasmodium falciparum and P. vivax, but also the simian malaria P. knowlesi, the chimpanzee malaria P. reichenowi, bird malarias such as P. elongatum and P. gallinaceum, and the rodent malarias, principally P. yoelii and P. berghei. Malaria merozoites have a plasma membrane and the basic cellular machinery of typical eukaryotic cells, including a nucleus, endoplasmic reticulum, Golgi network, ribosomes, and mitochondria. As a merozoite begins to invade an red blood cells (RBCs), an internal membrane-lined invasion pit develops. The whole process of merozoite invasion can be divided into three or four distinct phases with a number of ultrastructural alterations and molecular events attributed to each phase, with an untold number of others likely to be discovered in the future. Merozoites must first be released from the wornout, hemoglobin-depleted, and extensively altered erythrocyte that hosted their development. Although many proteins have been identified in the spheroidal dense bodies of Toxoplasma gondii, only a few proteins besides ring-infected erythrocyte surface antigen (RESA) have been located in the dense bodies of Plasmodium.
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Generalized diagrammatic representation of a merozoite showing the main structural features and organelles and also depicting the process by which newly formed micronemes are translocated along the microtubules to their placement at the apical pole (Bannister et al., 2003).
Generalized diagrammatic representation of a merozoite showing the main structural features and organelles and also depicting the process by which newly formed micronemes are translocated along the microtubules to their placement at the apical pole (Bannister et al., 2003).
Electron micrographs of P. vivax (a) and P. knowlesi (b) merozoites, showing the main structural features and organelles, as also detailed in the schematic shown in Fig. 1 .The P. knowlesi parasite was obtained from an infected rhesus macaque and prepared for EM morphology fixation at the Emory Vaccine Center at the Yerkes National Primate Research Center. (The photograph of P. vivax was produced with assistance from Michael J. Stewart and is reprinted from Galinski and Barnwell [1996], with permission from the publisher.)
Electron micrographs of P. vivax (a) and P. knowlesi (b) merozoites, showing the main structural features and organelles, as also detailed in the schematic shown in Fig. 1 .The P. knowlesi parasite was obtained from an infected rhesus macaque and prepared for EM morphology fixation at the Emory Vaccine Center at the Yerkes National Primate Research Center. (The photograph of P. vivax was produced with assistance from Michael J. Stewart and is reprinted from Galinski and Barnwell [1996], with permission from the publisher.)
(a) EM featuring the triple membranes and surface coat of the P. vivax merozoite shown in Fig. 2 with a tufted or spiked appearance. (b) Schematic representation of the merozoite membrane pellicle, consisting of the inner membrane complex, plasma membrane with connecting filaments, and a fibril bundled surface coat, as observed in Bannister et al. (1986b) .
(a) EM featuring the triple membranes and surface coat of the P. vivax merozoite shown in Fig. 2 with a tufted or spiked appearance. (b) Schematic representation of the merozoite membrane pellicle, consisting of the inner membrane complex, plasma membrane with connecting filaments, and a fibril bundled surface coat, as observed in Bannister et al. (1986b) .
Electron micrograph of a mature P. knowlesi schizont with merozoites surrounding the residual body and their apical ends facing outwards. Note that the PVM still appears intact at this late stage of development. Caveola vesicle complex structures (CVC; the basis of Schüffner's stippling) ( Coatney et al., 1971 ) can also be observed at the surface of the infected red blood cell membrane.The P. knowlesi parasite was obtained from an infected rhesus macaque and prepared for EM morphology fixation at the Emory Vaccine Center at Yerkes.
Electron micrograph of a mature P. knowlesi schizont with merozoites surrounding the residual body and their apical ends facing outwards. Note that the PVM still appears intact at this late stage of development. Caveola vesicle complex structures (CVC; the basis of Schüffner's stippling) ( Coatney et al., 1971 ) can also be observed at the surface of the infected red blood cell membrane.The P. knowlesi parasite was obtained from an infected rhesus macaque and prepared for EM morphology fixation at the Emory Vaccine Center at Yerkes.
EM invasion sequence of P. knowlesi merozoites. (a) Apically attached merozoite (cytochalasin B treated). (b) Invading merozoite with moving junction indicated. (c) Newly invaded, fully enveloped merozoite.The parasite preparations for panels a and c were generated for EM morphology fixation at the Emory Vaccine Center at the Yerkes National Primate Research Center. Figure 5b was contributed by Lawrence H. Bannister.
EM invasion sequence of P. knowlesi merozoites. (a) Apically attached merozoite (cytochalasin B treated). (b) Invading merozoite with moving junction indicated. (c) Newly invaded, fully enveloped merozoite.The parasite preparations for panels a and c were generated for EM morphology fixation at the Emory Vaccine Center at the Yerkes National Primate Research Center. Figure 5b was contributed by Lawrence H. Bannister.
Schematic representing the DBL, RBL, and AMA-1 protein families. Several members of each family are depicted with their predominant features highlighted, as indicated by the key at the bottom of the figure.
Schematic representing the DBL, RBL, and AMA-1 protein families. Several members of each family are depicted with their predominant features highlighted, as indicated by the key at the bottom of the figure.