Publications by authors named "Freddy Frischknecht"

Productive invasion of hepatocytes by Plasmodium sporozoites is a key step of infection. The parasites traverse hepatocytes before targeting one of them to form a parasitophorous vacuole for parasite expansion. Schepis et al.

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Host cell exit is a critical step in the life-cycle of intracellular pathogens, intimately linked to barrier penetration, tissue dissemination, inflammation, and pathogen transmission. Like cell invasion and intracellular survival, host cell exit represents a well-regulated program that has evolved during host-pathogen co-evolution and that relies on the dynamic and intricate interplay between multiple host and microbial factors. Three distinct pathways of host cell exit have been identified that are employed by three different taxa of intracellular pathogens, bacteria, fungi and protozoa, namely (i) the initiation of programmed cell death, (ii) the active breaching of host cellderived membranes, and (iii) the induced membrane-dependent exit without host cell lysis.

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Over the past decade, major advances in imaging techniques have enhanced our understanding of Plasmodium spp. parasites and their interplay with mammalian hosts and mosquito vectors. Cryoelectron tomography, cryo-X-ray tomography and super-resolution microscopy have shifted paradigms of sporozoite and gametocyte structure, the process of erythrocyte invasion by merozoites, and the architecture of Maurer's clefts.

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Malaria parasites undergo a complex life cycle between their hosts and vectors. During this cycle the parasites invade different types of cells, migrate across barriers, and transfer from one host to another. Recent literature hints at a misunderstanding of the difference between active, parasite-driven migration and passive, circulation-driven movement of the parasite or parasite-infected cells in the various bodily fluids of mosquito and mammalian hosts.

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Apicomplexa are obligate intracellular parasites that cause several human and veterinary diseases worldwide. In contrast to most intracellular pathogens these protozoans are believed to invade a rather passive host cell in a process, that is, tightly linked to the ability of the parasites to move by gliding motility. Indeed specific inhibitors against components of the gliding machinery and the analysis of knockdown mutants demonstrate a linkage of gliding motility and invasion.

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Unicellular parasites are of high medical relevance as they cause such devastating diseases as malaria or sleeping sickness. Besides the search for improved treatments, research on these parasites is valuable as they constitute interesting model cells to study basic processes of life. They can also serve as valuable reality checks for our presumed understanding of biological processes that emerge from the study of human or yeast cells, as our common ancestor with many parasites is much older than the one with yeast.

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Neutrophils are the most crucial cells for early defence against infections. When appropriately activated, they can kill obligate intracellular pathogens such as Leishmania. However, once the phagocytotic killing has been evaded, neutrophils can serve as host cells for Leishmania.

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Recent years have seen tremendous progress in our understanding of malaria parasite molecular biology. To a large extent, this progress follows significant developments in genetic, molecular and chemical tools available to study the malaria parasites and related Apicomplexa, in particular Toxoplasma gondii. One area of major advancement has been in understanding parasite host-cell invasion, a process that utilizes several essential molecular mechanisms that are conserved across the different lifecycle stages.

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Animal skin separates the inner world of the body from the largely hostile outside world and is actively involved in the defence against microbes. However, the skin is no perfect defence barrier and many microorganisms have managed to live on or within the skin as harmless passengers or as disease-causing pathogens. Microbes have evolved numerous strategies that allow them to gain access to the layers underneath the epidermis where they either multiply within the dermis or move to distant destinations within the body for replication.

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Over the millennia, pathogens have coevolved with their hosts and acquired the ability to intercept, disrupt, mimic, and usurp numerous signaling pathways of those hosts. The study of host/pathogen interactions thus not only teaches us about the intricate biology of these parasitic invaders but also provides interesting insights into basic cellular processes both at the level of the individual cell and more globally throughout the organism. Host/pathogen relationships also provide insights into the evolutionary forces that shape biological diversity.

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The study of pathogens and their interactions with host cells has advanced hand-in-hand with developments in optical microscopy. Whereas microbiology benefits enormously from modern imaging technologies, for example, digital imaging and confocal microscopy, it also presents unique challenges. To overcome these, microbiologists are adept at customising imaging methods, and recently there have been studies using state-of-the-art quantitative imaging methods to probe host-pathogen interactions at the single-cell level.

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A new view into the life of malaria parasites is now possible owing to recent advances in imaging techniques and to the generation of tagged parasites. Insights into how parasites interact with their insect vectors and mammalian hosts have been gained by the study of various parasitic forms in their natural environment. Quantitative analysis of Plasmodium ookinete motility has revealed different modes of motility in parasite invasion of the mosquito gut and the extrusion of invaded gut cells from the epithelium.

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The fusion of cell biology with microbiology has bred a new discipline, cellular microbiology, in which the primary aim is to understand host-pathogen interactions at a tissue, cellular and molecular level. In this context, we require techniques allowing us to probe infection in situ and extrapolate quantitative information on its spatiotemporal dynamics. To these ends, fluorescent light-based imaging techniques offer a powerful tool, and the state-of-the-art is defined by paradigms using so-called multidimensional (multi-D) imaging microscopy.

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The Wiskott-Aldrich syndrome protein family member N-WASP is a key integrator of the multiple signalling pathways that regulate actin polymerization via the Arp2/3 complex. Our previous studies have shown that N-WASP is required for the actin-based motility of vaccinia virus and is recruited via Nck and WIP. We now show that Grb2 is an additional component of the vaccinia actin tail-forming complex.

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