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Your search keyword '"Matthew W. A. Dixon"' showing total 2 results
Start Over Author "Matthew W. A. Dixon" Journal biochemical journal
2 results on '"Matthew W. A. Dixon"'

1. Nanobodies against Pfs230 block Plasmodium falciparum transmission

Author

Melanie H. Dietrich, Mikha Gabriela, Kitsanapong Reaksudsan, Matthew W. A. Dixon, Li-Jin Chan, Amy Adair, Stephanie Trickey, Matthew T. O'Neill, Li Lynn Tan, Sash Lopaticki, Julie Healer, Sravya Keremane, Alan F. Cowman, and Wai-Hong Tham

Subjects
Plasmodium falciparum, Protozoan Proteins, Animals, Humans, Antibodies, Protozoan, Antigens, Protozoan, Cysteine, Cell Biology, Single-Domain Antibodies, Molecular Biology, Biochemistry, Malaria
Abstract

Transmission blocking interventions can stop malaria parasite transmission from mosquito to human by inhibiting parasite infection in mosquitos. One of the most advanced candidates for a malaria transmission blocking vaccine is Pfs230. Pfs230 is the largest member of the 6-cysteine protein family with 14 consecutive 6-cysteine domains and is expressed on the surface of gametocytes and gametes. Here, we present the crystal structure of the first two 6-cysteine domains of Pfs230. We identified high affinity Pfs230-specific nanobodies that recognized gametocytes and bind to distinct sites on Pfs230, which were isolated from immunized alpacas. Using two non-overlapping Pfs230 nanobodies, we show that these nanobodies significantly blocked P. falciparum transmission and reduced the formation of exflagellation centers. Crystal structures of the transmission blocking nanobodies with the first 6-cysteine domain of Pfs230 confirm that they bind to different epitopes. In addition, these nanobodies bind to Pfs230 in the absence of the prodomain, in contrast with the binding of known Pfs230 transmission blocking antibodies. These results provide additional structural insight into Pfs230 domains and elucidate a mechanism of action of transmission blocking Pfs230 nanobodies.

Published
2022

2. Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II.

Author

Katherine E. Jackson, Tobias Spielmann, Eric Hanssen, Akinola Adisa, Frances Separovic, Matthew W. A. Dixon, Katharine R. Trenholme, Paula L. Hawthorne, Don L. Gardiner, Tim Gilberger, and Leann Tilley

Subjects
PLASMODIUM falciparum, PLASMODIUM, ERYTHROCYTES, BLOOD cells, STREPTOLYSIN
Abstract

Plasmodium falciparum develops within the mature RBCs (red blood cells) of its human host in a PV (parasitophorous vacuole) that separates the host cell cytoplasm from the parasite surface. The pore-forming toxin, SLO (streptolysin O), binds to cholesterol-containing membranes and can be used to selectively permeabilize the host cell membrane while leaving the PV membrane intact. We found that in mixtures of infected and uninfected RBCs, SLO preferentially lyses uninfected RBCs rather than infected RBCs, presumably because of differences in cholesterol content of the limiting membrane. This provides a means of generating pure preparations of viable ring stage infected RBCs. As an alternative permeabilizing agent we have characterized EqtII (equinatoxin II), a eukaryotic pore-forming toxin that binds preferentially to sphingomyelin-containing membranes. EqtII lyses the limiting membrane of infected and uninfected RBCs with similar efficiency but does not disrupt the PV membrane. It generates pores of up to 100 nm, which allow entry of antibodies for immunofluorescence and immunogold labelling. The present study provides novel tools for the analysis of this important human pathogen and highlights differences between Plasmodium-infected and uninfected RBCs. [ABSTRACT FROM AUTHOR]

Published
2007
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