Kai Matuschewski

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..Developmental up-regulation of specific mRNAs in the infectious transmission stage of Plasmodium indicates that their translation products may have unique roles in hepatocyte infection and/or development of liver stages...

..If confirmed in residents of malaria-endemic areas, periodic prophylaxis with safe and affordable antibiotics may offer a powerful shortcut toward a needle-free surrogate malaria immunization strategy...

..Together, our results show that the CP beta-subunit exerts an essential role in the insect vector before malaria transmission to the mammalian host. The vital role is restricted to fast locomotion, as displayed by Plasmodium sporozoites...

..Further, these three sporozoite surface proteins also act in concert with actin filaments to organize efficient adhesion of the sporozoite prior to initiating motility and host cell invasion...

..Genetically attenuated liver stages may thus induce immune responses, which inhibit subsequent infection of the liver with WT parasites...

..The motile extracellular stages of Plasmodium parasites are an excellent in vivo model system for functional characterization of actin regulation in single cell eukaryotes...

..This study also exemplifies how Plasmodium reverse genetics combined with biochemical and structural analyses of orthologous proteins can offer a fast track toward systematic gene characterization in apicomplexan parasites...

..Pharmacological inhibition of liver-stage parasites in the rodent malaria model offers a potential fast track toward development of a vaccine that targets parasites in preerythrocytic stages...

..We propose that arthropod-transmitted apicomplexan parasites specifically express secretory factors, such as SIAP-1, that mediate efficient oocyst exit and migration to the salivary glands...

..These findings establish the basic immune mechanisms underlying protection induced by genetically attenuated Plasmodium parasites and substantiate their use as vaccines against malaria...

..We propose that S6 functions together with TRAP/MIC2 family invasins to direct fast, efficient and specific cell entry and, ultimately, life cycle progression of the malaria sporozoite...

..Here, we review the basis, evidence and targets for whole-cell-based vaccination strategies against the liver stage bottleneck in Plasmodium infections and discuss preclinical and clinical research opportunities...

..In addition, these sporozoites can be used to quantify sporozoites deposited in subcutaneous tissue during natural infection...

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..This article discusses recent work, mostly done with rodent malaria parasites, that has contributed to a better understanding of the sporozoites' complex biology and which has opened up new avenues for future sporozoite research...

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..This previously unrecognized immunological benefit might also open new opportunities for population-wide presumptive drug administration as an adjunct malaria control tool...

..These findings have important implications for the development of genetically attenuated parasites as a vaccine approach...

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..This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible...

..In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver...

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..Although TLP is expressed in invasive stages, targeted gene disruption revealed a nonvital role during life cycle progression. This is the first genetic analysis of TLP, encoding a redundant TRAP family invasin, in the malaria parasite...

..The promises and hurdles of the different tracks towards an effective and affordable vaccine against malaria are discussed...

..However, we are only just beginning to discover the triggers that initiate gametocytogenesis and the developmental programs that drive sexual development...

..Unique properties of the individual components suggest that the rational design of motility inhibitors may lead to new intervention strategies to combat some of the most devastating human and livestock diseases...

..As these modules are also present in other members of the TRAP family of proteins in Apicomplexa, they may account for the capacity of these parasites to enter many cell types of phylogenetically distant origins...

..On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate...

..Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies...

..In this article, we summarize our current knowledge of Plasmodium microfilament dynamics and describe its potential players...

..Parasite actin polymers that support transmembrane receptors are pulled, by myosin interaction, backwards along the parasite periphery, resulting in forward movement...

..The combination of enhanced transfection efficiency and a versatile rodent model provides a basis for the further development of novel tools for high throughput genome manipulation...

..The actin/TRAP complex is then redistributed by the stationary MyoA from the anterior to the posterior end of the zoite, leading to its forward movement on a substrate or to penetration of a host cell...