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The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.
The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.
To a degree not widely recognized, some naturalized and invasive plants increase the risks to human health by enhancing the proliferation of vectors of virulent human parasites. These potential risks are restricted by neither ecosystem nor geography. The dense, floating mats of the tropical South American invasive macrophyte Eichhornia crassipes (water hyacinth) creates habitat for larvae of the dipteran vectors of Plasmodium spp., the causative agents of malaria, and other parasites. In Africa, the South American shrub Lantana camara (lantana) provides suitable habitat in otherwise treeless areas for dipteran vectors (Glossina spp.) of protozoans (Trypanosoma spp.) that cause trypanosomiasis. In the eastern United States, proliferation of the invasive Berberis thunbergii provides questing sites for the blacklegged ticks that carry the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. Unanticipated health consequences will likely continue to emerge from new plant introductions. Hantaviruses are rodent-borne parasites that cause lethal hemorrhagic fevers in humans. Populations of rodent Hantavirus vectors in South America increase rapidly in response to fruit availability among masting, native bamboos. In the United States the omnivorous deer mouse Peromyscus maniculatus also carries Hantavirus (Sin Nombre Virus). The on-going escape of Asian frost-tolerant bamboos from cultivation raises the possibility of their becoming invaders - several have already become naturalized - and in turn providing a temporary food source for populations of infected native rodents. Proposed introductions of floating aquatic vascular species, species with masting reproduction and species that could occupy an unfilled niche in a new range deserve careful evaluation as catalysts of unintended species interactions, especially of human parasites.