Biology subjects

Brehm, K.

Publications and source records attributed to Brehm, K..

12 recordsLinked to original sources

bioRxiv2026

Inhibition of Hippo signalling disrupts germinative cell-cycle progression and larval development in Echinococcus multilocularis

The metacestode larval stage of Echinococcus multilocularis exhibits a remarkable capacity for sustained, infiltrative growth, driven by germinative cells, the parasite's only mitotically active cell population. Yet, despite this seemingly unlimited growth potential, cell proliferation and differentiation must remain tightly coordinated to maintain tissue organization and parasite development. Here, we identify and functionally investigate components of the Hippo signaling pathway, a conserved regulator of cellular growth and tissue homeostasis, in E. multilocularis. We identified the principal components of the canonical pathway, including a highly divergent Yorkie ortholog, and demonstrated an interaction between EmYorkie and the TEAD-family transcription factor EmScalloped. Both emhippo and emyorkie are expressed in proliferating germinative cells and in association with differentiated neural and muscle cells, suggesting functions beyond stem cell regulation. RNA interference targeting emyorkie enhanced metacestode vesicle formation without a detectable increase in EdU incorporation at the time point examined. Treatment with XMU-MP-1, an inhibitor originally developed against mammalian MST1/2 kinases, induced pronounced enlargement and multinucleation of germinative cells, some of which retained the capacity for DNA synthesis despite the absence of detectable phospho-histone H3 staining. Comparison with the Aurora kinase inhibitor MLN8237 revealed differences in the magnitude and concentration dependence of giant-cell formation and phosphor-histone H3 staining. Together, our findings provide evidence for a role of EmYorkie in early larval development and reveal pronounced effects of XMU-MP-1 on germinative-cell morphology and cell-cycle-associated processes, highlighting the potential importance of Hippo-associated signaling in this parasitic flatworm.

cell biology↗

bioRxiv2026

Persistence of regenerative stem cells provides a cellular basis for the parasitostatic activity of albendazole against Echinococcus multilocularis

Albendazole (ABZ) is the mainstay of chemotherapy for alveolar echinococcosis caused by the larval stage of Echinococcus multilocularis, but its activity is predominantly parasitostatic rather than parasiticidal. The cellular basis of this remarkable parasite persistence remains poorly understood. Here, we investigated the effects of sustained ABZ exposure on the germinative stem cells that drive metacestode growth and regeneration and examined whether differential beta-tubulin isoform usage could contribute to their drug susceptibility. ABZ rapidly impaired microtubule-dependent tegumental transport and caused pronounced damage to metacestode vesicles. In contrast, proliferative germinative cells (GC) persisted during prolonged and continuous ABZ exposure. Importantly, cells surviving 14 to 28 days of treatment retained developmental competence, regenerated metacestode vesicles following drug withdrawal, and, after extended exposure to 10 micromolar ABZ, remained capable of generating parasite tissue following transplantation into a permissive host. Transcriptomic and immunohistochemical analyses identified the Y200 containing beta tubulin isoform Tub2 as a major metacestode beta tubulin that is almost exclusively associated with the proliferative GC lineage. Tub2 was present in virtually all S phase cells, colocalized with established GC markers, localized to mitotic spindles, and Tub2+ cells persisted during prolonged ABZ and ABZSO exposure. Structural analysis further revealed an E198-Y200 interaction in Tub2, providing a structural correlate of the resistance-associated Y200 configuration. Together, these findings provide a cellular explanation for the predominantly parasitostatic activity of benzimidazoles against E. multilocularis. ABZ profoundly damages parasite tissue while sparing a regenerative cell compartment capable of re-establishing metacestode growth after drug withdrawal. They further identify GC-associated Tub2 as a plausible molecular contributor to this persistence and as a potential target for curative anti-Echinococcus chemotherapy.

cell biology↗

bioRxiv2026

A single-cell transcriptomic atlas of the Echinococcus multilocularis metacestode reveals cellular diversity and molecular specialization

The metacestode of Echinococcus multilocularis is the proliferative larval stage responsible for alveolar echinococcosis and displays remarkable capacities for long-term growth, regeneration and development within the host. Despite its medical relevance, the cellular composition and molecular organization of this stage remain incompletely characterized. Here, we generated the first single-cell transcriptomic atlas of the E. multilocularis metacestode, resolving 26 transcriptionally distinct cell populations. The atlas recovered the major cell types previously described in the germinal layer, including germinative, tegumental, muscle, neuronal and putative storage cells, and revealed substantial molecular heterogeneity within several of these compartments. In particular, germinative cells segregated into distinct transcriptional states, ranging from a population enriched in markers associated with an undifferentiated germinative state to populations displaying early tegumental- or muscle-associated transcriptional programs. Notably, one of these states was strongly enriched in an isolate retaining the capacity for brood capsule and protoscolex formation but was nearly absent from a developmentally deficient isolate, suggesting a possible association between germinative-cell heterogeneity and developmental competence. Differentiated populations likewise displayed distinct molecular specializations, including developmental signaling and extracellular-matrix programs in muscle cells, microtubule-associated and transporter expression in tegumental populations, and metabolic specialization in putative storage cells. Spatial validation by whole-mount in situ hybridization, EdU labeling and immunofluorescence established molecular markers for major cell populations and revealed stage-specific expression patterns between metacestodes and protoscoleces. Together, these data uncover an unexpected level of molecular and cellular heterogeneity within the morphologically simple metacestode germinal layer and establish a cell-resolved framework for investigating stem-cell organization, differentiation and developmental plasticity in this medically important parasite.

cell biology↗

bioRxiv2026

Comparative proteomics reveals a conserved core of tegumental proteins in parasitic flatworms.

Parasitic flatworms, including cestodes and trematodes, are covered by a specialized syncytial tegument that mediates nutrient uptake and host-parasite interactions. While the tegument of trematodes has been extensively characterized, its molecular composition in cestodes remains largely unknown. In this work, we performed a comparative proteomic analysis of the tegument of three cestode species, including larval and adult stages: Hymenolepis microstoma, Mesocestoides corti (syn. M. vogae) and Echinococcus multilocularis. Using stringent enrichment criteria relative to whole-worm extracts, we identified hundreds of tegument-enriched proteins in each species. Comparative analyses revealed a conserved core of tegumental proteins shared among all three species, including members of the Tegument Allergen-Like (TAL) family, vesicular trafficking components and calcium-sensing proteins, and identified candidates for nutrient uptake activities such as glucose and nucleoside transporters. Further comparative analyses revealed a set of shared tegumental proteins with the trematode Schistosoma mansoni, including conserved proteins that are specific to parasitic flatworms, supporting the existence of a conserved ancestral tegumental proteome. Finally, we confirmed tegumental expression of several candidate genes in H. microstoma and E. multilocularis, and demonstrated regionally restricted gene expression among tegumental cytons, suggesting functional specialization within the syncytial tegument. Altogether, these results reveal an evolutionarily conserved composition of the tegument of parasitic flatworms, providing a foundation for future work targeting this critical host-parasite interface.

cell biology↗

bioRxiv2025

Canonical WNT signalling governs Echinococcus metacestode development

Alveolar echinococcosis (AE) is a lethal zoonosis caused by infiltrative growth of the metacestode larva of the tapeworm Echinococcus multilocularis in host organs. We previously showed that the Echinococcus metacestode is an evolutionarily unique, broadly posteriorized tissue, leading us to hypothesize that canonical WNT (cWNT) signalling--which patterns the body axis across metazoans--might be critical for metacestode formation. Here, we report effective RNAi-mediated knockdown of the E. multilocularis {beta}-catenin gene (bcat-1), the central effector of cWNT signalling, in a primary parasite cell culture system that produces metacestode vesicles. bcat-1(RNAi) cultures were markedly impaired in vesicle formation, exhibited stem-cell hyperproliferation, and displayed disrupted muscle-fibre organisation. Genome-wide transcriptomics revealed a general anteriorization of gene expression, and in situ hybridization showed an overproduction of cells expressing head-inducing factors such as sfrp upon bcat-1 knockdown. Conversely, metacestode-specific genes--including the tegumental factors muc-1, TNFR, and antigen B--as well as the posterior marker post2b were significantly downregulated, consistent with the observed vesicle-formation defects. In situ analyses further identified anterior markers--frizzled-10, nou-darake, notum, and follistatin--that were overexpressed in bcat-1(RNAi) cultures and localized to the future anterior pole at the earliest stages of protoscolex formation. Finally, pharmacological inhibition of WNT signalling with pyrvinium pamoate caused complete loss of posterior tissue in Echinococcus protoscoleces, killed metacestode vesicles, and reduced stem-cell proliferation at nanomolar concentrations. Together, these findings establish a central role for cWNT signalling in directing Echinococcus body-axis formation and the posteriorization events driving metacestode growth within the host, providing insight into asexual parasite proliferation mediated by this biologically unique larval stage and pointing to potential targets for chemotherapy against AE. Author SummaryAlveolar echinococcosis (AE) is a lethal disease caused by the cancer-like growth of the metacestode larva of the tapeworm Echinococcus multilocularis. From a developmental perspective, the Echinococcus metacestode is an unusual biological structure and even atypical among tapeworms. Previous work indicated that metacestode formation involves re-patterning of the body axis, eliminating head structures and producing broadly posteriorized tissue. How this is controlled at the molecular and cellular levels, however, was unknown. In this study, we perturbed expression of the {beta}-catenin gene (bcat-1), a central regulator of canonical WNT signalling, using RNA interference (RNAi). bcat-1(RNAi) parasite cultures failed to generate metacestode vesicles and instead showed stem-cell hyperproliferation and muscle-cell distortion. Genes required for posteriorized metacestode tissue were downregulated, whereas genes directing head formation in adult worms (follistatin, sfrp, fz10, ndk) were upregulated, indicating a general anteriorization of the culture system. Pharmacological inhibition of WNT signalling with pyrvinium pamoate caused complete loss of posterior structures in protoscoleces, reduced stem-cell proliferation, and killed metacestode tissue. These findings identify {beta}-catenin and the canonical WNT pathway as crucial regulators of the posteriorization that underlies metacestode formation. Given that WNT signalling is deregulated in many human cancers and that small-molecule inhibitors are available, our results suggest new avenues for anti-AE drug development.

developmental biology↗

bioRxiv2024

Putative EGF ligand and receptor of Echinococcus multilocularis that are critical for parasite development

The neglected zoonosis alveolar echinococcosis (AE) is caused by infiltrative growth of the metacestode larval stage of the cestode Echinococcus multilocularis within host organs. We previously demonstrated that metacestode growth depends on the mitotic activity of a population of parasite stem cells, called germinative cells, but it is not yet clear which molecular mechanisms govern Echinococcus stem cell dynamics such as cell-cycle progression, self-renewal and differentiation. Based on previous reports showing that epidermal growth factor (EGF) signalling contributes to Echinococcus stem cell regulation, we herein characterized three EGF receptors of the parasite and demonstrated by RNAi and inhibitor assays that one of these, EmER1, is crucial for the development of metacestode vesicles from parasite stem cells. We also showed that EmER1 serves as a target for afatinib, an EGF receptor inhibitor with profound anti-parasitic activities in vitro and in vivo. By bioinformatic analyses and membrane-bound yeast two-hybrid assays, we identified a parasite-derived, neuregulin-like cognate ligand for EmER1, EmNRG, the expression of which is strongly upregulated in metacestode vesicles during clonal expansion of germinative cells. Furthermore, we demonstrate that RNAi knockdown of the EmNRG encoding gene drastically affects the ability of germinative cells to produce metacestode vesicles. We propose that EmNRG and EmER1 form a cognate ligand-receptor system utilized by E. multilocularis to regulate asymmetric versus symmetric division decisions of stem cells. These data are relevant for further studies into Echinococcus stem cell dynamics and for the development of EGF signalling-based anti-infectives against echinococcosis.

microbiology↗

bioRxiv2023

Establishment and application of unbiased in vitro drug screening assays for the identification of compounds against Echinococcus granulosus s.s.

Echinococcus multilocularis and E. granulosus s.l. are the causative agents of alveolar and cystic echinococcosis, respectively. Drug treatment options for these severe and neglected diseases are limited to benzimidazoles, which are not always efficacious, and adverse side effects are reported. Thus, novel and improved treatments are needed. In this study, the previously established platform for E. multilocularis in vitro drug assessment was adapted to E. granulosus s.s.. In a first step, in vitro culture protocols for E. granulosus s.s. were established. This resulted in the generation of large amounts of E. granulosus s.s. metacestode vesicles as well as germinal layer (GL) cells. In vitro culture of these cells formed metacestode vesicles displaying structural characteristics of metacestode vesicles generated in vivo. Next, drug susceptibilities of E. multilocularis and E. granulosus s.s. protoscoleces, metacestode vesicles and GL cells were comparatively assessed employing established assays including (i) metacestode vesicle damage marker release assay, (ii) metacestode vesicle viability assay, (iii) GL cell viability assay, and (iv) protoscolex motility assay. The standard drugs albendazole, buparvaquone, mefloquine, MMV665807, monepantel, niclosamide and nitazoxanide were included. MMV665807, niclosamide and nitazoxanide were active against the parasite in all four assays against both species. MMV665807 and monepantel were significantly more active against E. multilocularis metacestode vesicles, while albendazole and nitazoxanide were significantly more active against E. multilocularis GL cells. Albendazole displayed activity against E. multilocularis GL cells, but no effects were seen in albendazole-treated E. granulosus s.s. GL cells within five days. Treatment of protoscoleces with albendazole and monepantel had no impact on motility. Similar results were observed for both species with praziquantel and its enantiomers against protoscoleces. In conclusion, in vitro culture techniques and drug screening methods previously established for E. multilocularis were successfully implemented for E. granulosus s.s., allowing comparisons of drug efficacy between the two species.

pharmacology and toxicology↗

bioRxiv2022

Molecular characterization of a DyP-type peroxidase from the human parasitic cestode Echinococcus multilocularis

The lethal zoonosis alveolar echinococcosis is caused by the metacestode larval stage of the tapeworm Echinococcus multilocularis. During the chronic phase of the disease, metacestode tissue is growing infiltratively into liver tissue and provokes an immunes response of the host. Mechanisms of parasite defence against reactive oxygen species (ROS), which are produced during parasite growth and host immune responses, are incompletely understood so far. We herein describe the characterization of an Echinococcus Dyp (dye decolorizing) - type peroxidase, EmDyp, family members of which are typically expressed by bacteria and fungi. EmDyp showed significant homologies to bacterial and fungal Dyp peroxidases and recombinantly expressed EmDyp displayed profound enzymatic activity towards different substrates such as 3,3-diaminobenzidine or luminol. Furthermore, although structurally not being related to classical catalases, EmDyp showed catalase activity in respective activity gels. In situ hybridization experiments showed expression of the EmDyp expressing gene, emdyp, in the germinal layer of the metacestode as well as in the posterior region of the protoscolex, both in differentiated and in germinative (stem) cells of the parasite. Interestingly, RT-qPCR experiments demonstrated that emdyp expression is induced in the metacestode upon growth under aerobic conditions. Particularly high expression of emdyp was observed under in vivo growth conditions in jirds within the liver. These data indicate a role of EmDyp in the defence of the metacestode against host- and/or parasite-derived ROS during chronic alveolar echinococcosis. Since Dyp-type peroxidases are not encoded on the genomes of mammalian hosts for E. multilocularis, EmDyp might be used as a target molecule for developing novel therapeutics against the parasite.

molecular biology↗

bioRxiv2022

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

BackgroundThe potentially lethal zoonosis alveolar echinococcosis (AE) is caused by the metacestode larval stage of the tapeworm Echinococcus multilocularis. Current AE treatment options are limited and rely on surgery as well as on chemotherapy involving benzimidazoles (BZ). BZ treatment, however, is parasitostatic only, must be given for prolonged time periods, and is associated with adverse side effects. Novel treatment options are thus urgently needed. Methodology/Principal findingsBy applying a broad range of kinase inhibitors to E. multilocularis stem cell cultures we identified the proto-oncogene PIM kinase as a promising target for anti-AE chemotherapy. The gene encoding the respective E. multilocularis ortholog, EmPIM, was characterized and in situ hybridization assays indicated its expression in parasite stem cells. By yeast two-hybrid assays we demonstrate interaction of EmPIM with E. multilocularis CDC25, indicating an involvement of EmPIM in parasite cell cycle regulation. Small molecule compounds SGI-1776 and CX-6258, originally found to effectively inhibit human PIM kinases, exhibited detrimental effects on in vitro cultured parasite metacestode vesicles and prevented the formation of mature vesicles from parasite stem cell cultures. To improve compound specificity for EmPIM, we applied a high throughput in silico modelling approach, leading to the identification of compound Z196138710. When applied to in vitro cultured metacestode vesicles and parasite cell cultures, Z196138710 proved equally detrimental as SGI-1776 and CX-6258, but displayed significantly reduced toxicity towards human HEK293T and HepG2 cells. Conclusions/SignificanceRepurposing of kinase inhibitors initially designed to affect mammalian kinases for helminth disease treatment is often hampered by adverse side effects of respective compounds on human cells. Here we demonstrate the utility of high throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. We propose EmPIM as a promising target for respective approaches towards AE treatment. Author summaryThe larva of the tapeworm E. multilocularis grows tumor-like within the host liver, thus causing the lethal disease alveolar echinococcosis (AE). Anti-parasitic treatment relies on chemotherapy with benzimidazoles, which do not kill the parasite and must be applied for years. As druggable enzymes with key functions in growth control, protein kinases are promising drug targets and many kinase inhibitors have been identified during cancer research. Optimized for binding to human kinases, however, repurposing of such drugs for parasitic disease treatment is associated with adverse side effects. Herein, the authors applied an in silico approach to identify small molecule compounds that show higher specificity for a parasite kinase, EmPIM, over its mammalian homologs. The authors demonstrate expression of EmPIM in Echinococcus stem cells, which are the drivers of parasite growth, and show that mammalian PIM kinase inhibitors SGI-1776 and CX-6258 also affect parasite development in vitro. Finally, they show that one of the in silico screened compounds is equally effective against the parasite as SGI-1776 and CX-6258, but significantly less toxic to human cells. These results demonstrate the utility of in silico approaches to identify parasite-specific kinase inhibitors.

microbiology↗

bioRxiv2019

A secreted Echinococcus multilocularis activin A homologue promotes regulatory T cell expansion

BackgroundAlveolar echinococcosis (AE), caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis, is a chronic zoonosis associated with significant modulation of the host immune response. A role of regulatory T-cells (Treg) in generating an immunosuppressive environment around the metacestode during chronic disease has been reported, but the molecular mechanisms of Treg induction by E. multilocularis remain elusive so far.\n\nMethodology/Principal findingsWe herein demonstrate that excretory/secretory (E/S) products of the E. multilocularis metacestode promote the formation of Foxp3+ Treg from CD4+ T-cells in vitro in a TGF-{beta}-dependent manner. We also show that host T-cells secrete elevated levels of the immunosuppressive cytokine IL-10 in response to metacestode E/S products. Within the E/S fraction of the metacestode we identified an E. multilocularis activin A homolog (EmACT) that displays significant similarities to mammalian Transforming Growth Factor-{beta} (TGF-{beta})/activin subfamily members. EmACT obtained from heterologous expression promoted host TGF-{beta}-driven CD4+ Foxp3+ Treg conversion in vitro. Furthermore, like in the case of metacestode E/S products, EmACT-treated CD4+ T-cells secreted higher levels of IL-10. These observations suggest a contribution of EmACT in the in vitro expansion of Foxp3+ Treg by the E. multilocularis metacestode. Using infection experiments we show that intraperitoneally injected metacestode tissue expands host Foxp3+ Treg, confirming the expansion of this cell type in vivo during parasite establishment.\n\nConclusions/SignificanceIn conclusion, we herein show that E. multilocularis larvae secrete a factor with clear structural and functional homologies to mammalian activin A. Like its mammalian homolog, this protein induces the secretion of IL-10 by T-cells and contributes to the expansion of TGF-{beta}-driven Foxp3+ Treg, a cell type that has been reported crucial for generating a tolerogenic environment to support parasite establishment and proliferation.\n\nAUTHOR SUMMARYThe metacestode larval stage of the tapeworm E. multilocularis grows infiltratively, like a malignant tumor, within the organs of its human host, thus causing the lethal disease alveolar echinococcosis (AE). Immunosuppression plays an important role in both survival and proliferation of the metacestode, which mainly depends on factors that are released by the parasite. These parasite-derived molecules are potential targets for developing new anti-echinococcosis drugs and/or improving the effectiveness of current therapies. Additionally, an optimized use of such factors could help minimize pathologies resulting from over-reactive immune responses, like allergies and autoimmune diseases. The authors herein demonstrate that the E. multilocularis metacestode releases a protein, EmACT, with significant homology to activin A, a cytokine that might support host TGF-{beta} in its ability to induce the generation of immunosuppressive regulatory T-cells (Treg) in mammals. Like its mammalian counterpart, EmACT was associated with the expansion of TGF-{beta}-induced Treg and stimulated the release of elevated amounts of immunosuppressive IL-10 by CD4+ T-cells. The authors also demonstrate that Treg are locally expanded by the metacestode during an infection of mice. These data confirm an important role of Treg for parasite establishment and growth during AE and suggest a potential role of EmACT in the expansion of these immunosuppressive cells around the parasite.

immunology↗

bioRxiv2019

Cue-induced effects on decision-making distinguish subjects with gambling disorder from healthy controls

While an increased impact of cues on decision-making has been associated with substance dependence, it is yet unclear whether this is also a phenotype of non-substance related addictive disorders, such as gambling disorder. To better understand the basic mechanisms of impaired decision-making in addiction, we investigated whether cue-induced changes in decision-making could distinguish gambling disorder (GD) from healthy control (HC) subjects. We expected that cue-induced changes in gamble acceptance and specifically in loss aversion would distinguish GD from HC subjects. 30 GD subjects and 30 matched HC subjects completed a mixed gambles task where gambling and other emotional cues were shown in the background. We used machine learning and classification to carve out the importance of cue-dependency of decision-making and of loss aversion for distinguishing GD from HC subjects. Cross-validated classification yielded an area under the receiver operating curve (AUC-ROC) of 68.9% (p=0.002). Applying the classifier to an independent sample yielded an AUC-ROC of 65.0% (p=0.047). As expected, the classifier used cue-induced changes in gamble acceptance to distinguish GD from HC. Especially increased gambling during the presentation of gambling cues was characteristic of GD subjects. However, unexpectedly, cue-induced changes in loss aversion were irrelevant for distinguishing GD from HC subjects. To our knowledge, this is the first study to investigate the classificatory power of addiction-relevant behavioral task parameters when distinguishing GD from HC subjects. The results indicate that cue-induced changes in decision-making are a characteristic feature of addictive disorders, independent of a substance of abuse.

neuroscience↗

bioRxiv2018

The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction

BackgroundAlveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of the tapeworm Echinococcus multilocularis. The infection is characterized by tumour-like growth of the metacestode within the host liver, leading to extensive fibrosis and organ-failure. The molecular mechanisms of parasite organ tropism towards the liver and influences of liver cytokines and hormones on parasite development are little studied to date.\n\nMethodology/Principal findingsWe show that the E. multilocularis larval stage expresses three members of the fibroblast growth factor (FGF) receptor family with homology to human FGF receptors. Using the Xenopus expression system we demonstrate that all three Echinococcus FGF receptors are activated in response to human acidic and basic FGF, which are present in the liver. In all three cases, activation could be prevented by addition of the tyrosine kinase inhibitor BIBF 1120, which is used to treat human cancer. At physiological concentrations, acidic and basic FGF significantly stimulated the formation of metacestode vesicles from parasite stem cells in vitro and supported metacestode growth. Furthermore, the parasites mitogen activated protein kinase signalling system was stimulated upon addition of human FGF. The survival of metacestode vesicles and parasite stem cells were drastically affected in vitro in the presence of BIBF 1120.\n\nConclusions/SignificanceOur data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and host-parasite interaction in AE. Furthermore, our data indicate that the parasites FGF signalling systems are promising targets for the development of novel drugs against AE.\n\nAuthor summaryTo ensure proper communication between their different cell populations, animals rely on secreted hormones and cytokines that act on receptors of target cells. Most of the respective cytokines, such as FGFs, evolved over 500 million years ago and are present in similar form in all animals, including parasitic worms. The authors of this study show that the metacestode larva of the tapeworm E. multilocularis, which grows like a malignant tumor within the host liver, expresses molecules with homology to FGF receptors from mammals. The authors show that human FGF, which is abundantly present in the liver, stimulates metacestode development and that all parasite FGF receptors are activated by human FGF, despite 500 million years of evolutionary distance between both systems. This indicates that cells of the Echinococcus metacestode can directly communicate with cells of the mammalian host using evolutionarily conserved signaling molecules. This mode of host-pathogen interaction is unique for helminths and does not occur between mammals and single-celled pathogens such as protozoans or bacteria. The authors finally demonstrate that BIBF 1120, a drug used to treat human cancer, targets the Echinococcus FGF receptors and leads to parasite death. This opens new ways for the development of anti-parasitic drugs.

zoology↗