The institute deals with parasitic diseases of domestic and farm animals, and of humans, and is involved in teaching, research and diagnostic services and consulting.
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.
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.
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.
Wir gratulieren Prof. Dr. Caroline Frey zur Haller Medaille.
Prof. Dr. Andrew Hemphill received the titel Visiting Professor at the National University La Plata (Argentina). Congratulations Andrew!
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.
Prof. Dr. Andrew Hemphill received the titel Honorary Professor at the Complutense University of Madrid. Congratulations Andrew!
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.
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.
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.
The Annual Report 2018 of the Institute of Parasitology is available online now.
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”
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!
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.
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.
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”
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.
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“.
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.
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.
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.
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.
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.
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!
We congratulate Reto Rufener to his successful PhD half-time presentation with the title “Echinococcus multilocularis: Studies on drugs and metabolism”