Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis

In this invited review article we summarize our most recent findings in the search for novel chemotherapies against alveolar echinococcosis. In particular, we focus on the anti-malarial mefloquine, which showed promising activities in vitro and in different mouse models of the disease.

Caroline Frey vice president of ESCCAP Switzerland

Caroline Frey is the new vice president of ESCCAP Switzerland. Congratulations!

Congratulations Dr. Ritler

We congratulate our PhD student Dominic Ritler to successfully defending his thesis "New ways to target the deadly parasite Echinococcus multilocularis"! Well done Dr. Dominic Ritler.

PhD half-time Nicoleta Anghel

We congratulate Nicoleta Anghel to her successful PhD half-time presentation with the title “Studies on activity and safety of novel compounds against apicomplexan parasites”

Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg infection in C57BL/6 mice

We present a comprehensive analysis of the hepatic microRNAs (miRNAs) transcriptome at early stage of experimental primary alveolar echinococcosis. Expression of miRNAs was significantly altered in infected livers; miRNAs were mainly down regulated. Target genes of the most extensively down-regulated miRNAs were involved in angiogenesis and fatty acid synthesis. Furthermore, expression of key angiogenic and lipogenic genes was higher in infected livers. Some precursor miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. Further research on how E. multilocularis contribute to the regulation of the hepatic miRNA transcriptome is needed.

Whole genome sequencing of bovine, feline and porcine Tritrichomonas foetus strains

Tritrichomonas foetus is a protozoan parasite that colonizes the reproductive tract of cattle, the gastrointestinal tract of cats, or the nasal cavity of pigs. We generated whole genome sequencing data from bovine, feline and porcine T. foetus strains. These data clearly indicated a close phylogenetic relationship between bovine and porcine T. foetus but a remarkable genetic distinctness of these two strains from the feline strain. Our comparative genome sequencing approach granted deep insights into the genetic diversity of T. foetus in relation to the different host origins of the parasite. Furthermore, our study identified a large number of SNP- and indel-containing sequences that may be useful molecular markers for future epidemiological studies aimed at the elucidation of the transmission patterns of T. foetus within different host species.

Congratulations Dr. Rufener

We congratulate our PhD student Reto Rufener to successfully defending his thesis "New drugs against Echinococcus multilocularis - targeting the energy metabolism"! Very well done Dr. Reto Rufener.

Metabolic profiling of Giardia lamblia strains

In Giardia lamblia, enzymes involved in anaerobic nitro reduction have been investigated in detail as potential targets. Their role within the normal metabolic context is, however, not understood. Using 1H HR-MAS NMR spectroscopy, we analyzed the metabolomes of G. lamblia trophozoites overexpressing three nitroreductases (NR1 – NR3) and thioredoxin reductase (TrxR), most likely a scavenger of reactive oxygen species. We compared the patterns to convenient controls and to the situation in the strain nitro drug resistant strain C4 where NR1 is downregulated. Trophozoites overexpressing NR1 presented a distinct pattern of nine metabolites, in particular arginine catabolites, differing from the respective controls. This pattern matched a differential pattern between wildtype and strain C4. This suggests that NR1 interferes with arginine and thus energy metabolism. The exact metabolic function of NR1 (and the other nitroreductases) remains to be elucidated.

In vitro metabolomic footprint of the Echinococcus multilocularis metacestode

We analyzed the unknown metabolic footprint of the parasite E. multilocularis and identified that the metacestode of E. multilocularis consumed glucose, and, surprisingly, threonine, whereas it released succinate, acetate, and alanine as major fermentation end products. This study provides the basis for analyses of potentially targetable pathways for future drug development.

Die Haller Medaille wird an Frau Prof. Dr. Caroline Frey verliehen

Wir gratulieren Prof. Dr. Caroline Frey zur Haller Medaille.

Andrew Hemphill Honorary Professor at National University of La Plata, Argentina

Prof. Dr. Andrew Hemphill received the titel Visiting Professor at the National University La Plata (Argentina). Congratulations Andrew!

Britta Lundström-Stadelmann elected president of Swiss Society of Tropical Medicine and Parasitology

Prof. Dr. Britta Lundström-Stadelmann was elected president of the Swiss Society of Tropical Medicine and Parasitology at the society's general assembly in Lausanne on Sept 19.

Andrew Hemphill Honorary Professor at Complutense University of Madrid

Prof. Dr. Andrew Hemphill received the titel Honorary Professor at the Complutense University of Madrid. Congratulations Andrew!

Development and comparative evaluation of different LAMP and PCR assays for coprological diagnosis of feline tritrichomonosis

The protozoan parasite Tritrichomonas foetus may cause severe diarrhea in cats all over the world. We developed a
loop-mediated isothermal amplification (LAMP) as well as a real-time PCR assay allowing a reliable and direct coprological
diagnosis of T. foetus infections. The LAMP assay may also serve as practical molecular tools to perform epidemiological
studies on feline tritrichomonosis under simple laboratory conditions.

Nitroreductases of bacterial origin in Giardia lamblia: Potential role in detoxification of xenobiotics

The anaerobic parasite Giardia lamblia, causative agent of persistent diarrhea, contains a family of nitroreductases that
may provide at least two evolutionary advantages namely a higher potential to recycle electron acceptors for the
(fermentative) energy and intermediary metabolism, and the possibility to inactivate toxic xenobiotics produced by
microorganisms living in concurrence inside the intestinal habitat.

Emerging issues for zoonotic Echinococcus species – engaging old enemies in a changing environment

In this special issue of the Journal Food and Waterborne Parasitology the guest editors Caroline Frey, Emely Jenkins, and Britta Lundström-Stadelmann present a series of invited papers on echinococcosis covering topics from molecular markers of emergence, diagnostics in both definitive and intermediate hosts, treatment, to control strategies in definitive hosts.

Annual Repot 2018

The Annual Report 2018 of the Institute of Parasitology is available online now.

PhD half-time Dominic Ritler

We congratulate Dominic Ritler to his successful PhD half-time presentation with the title “Bullets against Echinococcus multilocularis: screening-based drug discovery and omics-based target identification”

SNSF Project Grant group Hemphill

Prof. A. Hemphill's project on "Effects of a double-edged sword: exploiting the interaction between immunity and chemotherapy in murine and ovine models of congenital neosporosis and toxoplasmosis" got approved by the Swiss National Science Foundation. Congratulations!

The importance of being parasiticidal… an update on drug development for the treatment of alveolar echinococcosis

In this review we give an update on drug development for the treatment of alveolar echinococcosis, the disease caused by the fox tapeworm Echinococcus multilocularis.

Directorship in Jobsharing

Prof. Dr. C. Frey and Prof. Dr. Lundström-Stadelmann elected as extraordinary Professors by the University of Bern and the Vetsuisse-Rat, sharing the directorship of the Institute of Parasitology Bern from August 1 2019 on.

PhD half-time Pablo Winzer

We congratulate Pablo Winzer to his successful PhD half-time presentation with the title “Molecular changes of Neosporacaninum treated with Calcium dependent protein kinase 1 inhibitor 1294 and implications on the immune response”

Targeting of the mitochondrion by dinuclear thiolato-bridged arene ruthenium complexes in cancer cells and in the apicomplexan parasite Neospora caninum

Ruthenium(II) complexes have attracted attention because of their favorable anti-cancer properties. In this paper, we report on the antiparasitic efficacy of dinuclear-thiolato bridged arene ruthenium complexes against the apicomplexan parasites N. caninum. We show that their activity and uptake can be correlated with their lipophilicity and we demonstrate their ability to selectively target the mitochondria not only in cancer cells, but also in the parasite. In vivo experiments also reveal that the compounds accumulated in liver and kidneys, but were absent from the brain. However, the compounds did not act as parasiticidal.

Karl-Enigk doctoral stipend

Congratulations to Dominic Ritler for the doctoral stipend form the Karl-Enigk-Stiftung for his work on “metabolomics host-pathogen interaction studies of the fox tapeworm Echinococcus multilocularis“.

Strongyloides stercoralis infection in imported and local dogs in Switzerland: from clinics to molecular genetics

This study reports on the diagnosis and genetic characterization of Strongyloides stercoralis infecting imported and locally born dogs in Switzerland. Some of the infected dogs presented severe disease, with diarrhoea, dehydration, vomiting, respiratory and/or neurologic signs, and needed hospitalisation. S. stercoralis isolated from three independent clinical cases exhibited an identical genetic background on the nuclear 18S rDNA (fragment involving hypervariable regions I and IV) and the mitochondrial cytochrome oxidase subunit I (cox1) loci, similar to that of zoonotic isolates from other geographical regions, and not to that of dog-adapted variants. Due to the clinical relevance and zoonotic potential of this parasite, the awareness of both diagnosticians and clinicians is strongly required.

Endochin-like quinolones for treatment of neosporosis

This paper reports that endochin-like quinolones, a group of cytochrome b Qi site inhibitors of the respiratory chain, were identified as highly potent compounds, exhibiting IC50 values against Neospora caninum in the sub-nanomolar range. In vivo, treatment of pregnant mice with ELQ-334, applied as prodrug for the highly active compound ELQ-316, clearly limited vertical transmission of N. caninum, and lead to significantly increased survival of offspring. This renders this compound class highly interesting for further development.

Repurposing of an old drug: activities of Buparvaquone against Echinococcus multilocularis

In this study we screened 400 compounds of the Medicines for Malaria Venture (MMV) pathogen box against the disease-causing metacestode stage of the fox tapeworm Echinococcus multilocularis. One of the most active compounds, buparvaquone, was shown to inhibit the mitochondrial complex III in isolated parasite cells. However, the drug was not active against the parasite in mice.

Recombinant vaccine against neosporosis

This study reports on the application of a polyvalent recombinant vaccine formulation, composed of three Neospora antigens that were physically linked to OprI, a bacterial outer membrane protein that acts as a Toll-like receptor 2 (TLR2) ligand. Conjugation to OprI modulates immunity to elicit a balanced Th1/Th2 response, which is not detrimental to pregnancy outcome, and at the same time mediates protection against clinical signs of neosporosis and vertical transmission in offspring mice.

PD-L1 inhibition against alveolar echinococcosis

In immunology, checkpoints inhibitors have become very atractive immunotherapeutics especially in cancer treatment (see respective Nobel prize award 2018). In parasitic diseases such as alveolar echinococcosis, where Treg-induced anergy is a hallmark of the host-parasite interplay, experimental abrogation of down-regulated immunity may be a way to immunologically treat this disease e.g. as a support of conventional therapy by albendazole medication. In a first respective study, we now elegantly documented how the parasite load could be significantly reduced upon inhibition of the PD-L1 pathway.

Communications Chemistry - Nature

A study published in Communications Chemistry – Nature shows that decoquinate derivatives are highly and selectively active against the causative agents of malaria, tuberculosis, toxoplasmosis and neosporosis. Andrew Hemphill and Joachim Müller from the Institute of Parasitology in Bern contributed to this paper by studying the impact of decoquinate derivatives against the parasites Toxoplasma gondii and Neospora caninum. Congratulations!

PhD half-time Reto Rufener

We congratulate Reto Rufener to his successful PhD half-time presentation with the title “Echinococcus multilocularis: Studies on drugs and metabolism”