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Intestinal infections with parasitic protozoa

Introduction

Intestinal infections with parasitic protozoa display a global distribution and can cause serious morbidity depending on the infectious agents and immune status of the patient. Even in resource-rich countries infections with parasitic protozoa constitute a serious problem, e.g. due to increasing development of resistance to standard therapies. The infections are primarily transmitted by oral ingestion of infectious dormant stages of the parasite (cysts) with contaminated food or contaminated water. Gut-associated parasitic protozoa are comprised of many different pathogen groups but Giardia duodenalis and Cryptosporidium ssp. are responsible for most of the notifiable parasitoses in Germany.

(A) Picture of G. duodenalis cysts. (B) Immunofluorescence microscopy of G. duodenalis trophozoite(A) Picture of G. duodenalis cysts (patient isolate), green: cyst wall, red: nucleic acids. (B) Immunofluorescence microscopy of G. duodenalis trophozoite (WB-C6), green: alpha-Tubulin, red: cell body, blue: cell nuclei. Source: (A) Klotz, C. 2011; (B) Hahn, J. 2013

The most frequent notifiable intestinal parasitosis, giardiasis, is caused by an infection with Giardia duodenalis (syn. G. intestinalis, G. lamblia). These flagellated organisms belong taxonomically to the diplomonads. The disease-associated proliferative stages (trophozoites) populate the epithelium of the anterior small intestine and can cause diarrhoeas with different symptoms. The disease has often a mild course and is self-limiting but can also have a serious chronic progression. Host factors, such as the immune status, age or nutritional status, and parasite virulence factors, both are responsible for the pathogenesis. The latter are, however, only insufficiently understood. G. duodenalis is comprised of at least 8 distinct genetic groups (assemblages A-H) and is also referred to as a ‘species complex’ since it is not clear yet whether these distinct genetic groups represent one single species. The human-pathogenic assemblages A and B have the broadest host spectrum and are not only found in humans but also in many domestic and wild animals. Whether and to what extent they should, therefore, be classified as potentially zoonotic is unclear.

We aim at a better understanding of virulence and pathogenicity mechanisms of intestinal parasitoses and at identifying the underlying factors in order to improve the current diagnostic and therapeutic strategies and to improve molecular approaches to study the epidemiology and find the answer to the question "Is autochthonous Giardiasis a zoonosis, yes or no?".

Functional epidemiology of Giardia duodenalis infections

Principle Investigator: Anton Aebischer and Christian Klotz

In this project a Giardia duodenalis database and biobank with clinical and environmental isolates is built up. Epidemiological data and relevant case information for clinical infections are collected and the parasites are isolated, as possible cultivated and centrally preserved. This is done in co-operation with partners from human and animal medicine institutions. Giardia isolates of this biobank are classified based on known molecular marker loci and new, possibly virulence-associated genes. Furthermore, functional tests are developed for potential virulence factors in order to identify possible correlations between sequence and function-types with the epidemiological data. Finally, the diagnostic potential of such correlations will be evaluated to clarify whether giardiasis in Germany is a zoonosis. The biobank will contribute to the infrastructure of zoonosis research in Germany and will be openly available also for interested third parties for further Giardia research projects.

Application of in vitro-models to investigate pathogen-host relationships of gastro-intestinal protozoa infections

Principle Investigator: Christian Klotz and Anton Aebischer

This project focuses on investigations of the molecular, immunological and cell biological mechanisms of pathogen-host interactions. The goal is to characterise mechanisms which are essential for the virulence and pathogenicity of gut-associated parasitic protozoa occurring in Germany, in order to identify new control and/or prevention approaches.

For most of the intestinal parasites there are no appropriate cell culture systems outside the host to adequately examine the parasites themselves or pathogen-host interactions. This applies particularly to disease-associated field isolates or novel pathogens for which sufficient models have not yet been developed. In order to counter this, the group deals with the establishment of novel stem cell based intestinal culture models to investigate these intestinal infections and the following topics with the primary focus on G. duodenalis infections:

  • Interactions of G. duodenalis with host cells, in particular intestinal epithelium cells and cells of the innate immune system.
  • Mode of action of potential virulence factors of G. duodenalis.
  • Immune modulation mechanisms by G. duodenalis.
  • Application of stem cell-based cell culture models for the investigation of gastrointestinal infections.

Date: 02.05.2019

Publications

  • Delgado Betancourt E, Hamid B, Fabian BT, Klotz C, Hartmann S, Seeber F (2019): From entry to early dissemination—Toxoplasma gondii's initial encounter with its host.
    Front. Cell. Infect. Microbiol. 9: 46. Epub Mar 5. doi: 10.3389/fcimb.2019.00046. more

  • Geus D, Sifft KC, Habarugira F, Mugisha JC, Mukampunga C, Ndoli J, Bayingana C, Sendegeya A, Martus P, Fraundorfer K, von Samson-Himmelstjerna G, Gahutu JB, Klotz C, Aebischer T, Mockenhaupt FP (2019): Co-infections with Plasmodium, Ascaris and Giardia among Rwandan schoolchildren.
    Trop. Med. Int. Health 24 (4): 409-420. Epub Jan 19. doi: 10.1111/tmi.13206. more

  • Rehbein S, Klotz C, Ignatius R, Müller E, Aebischer T, Kohn B (2019): Giardia duodenalis in small animals and their owners in Germany: A pilot study.
    Zoonoses Public Health 66 (1): 117–124. Epub 2018 Nov 20. doi: 10.1111/zph.12541. more

  • Chalmers RM, Pérez-Cordón G, Cacció SM, Klotz C et al.; participants of the Cryptosporidium genotyping workshop (EURO-FBP) (2018): Cryptosporidium genotyping in Europe: The current status and processes for a harmonised multi-locus genotyping scheme
    Exp. Parasitol. 191: 25–30. Epub Jun 13. doi: 10.1016/j.exppara.2018.06.004. more

  • Helmy YA, Spierling NG, Schmidt S, Rosenfeld UM, Reil D, Imholt C, Jacob J, Ulrich RG, Aebischer T, Klotz C (2018): Occurrence and distribution of Giardia species in wild rodents in Germany
    Parasit. Vectors 11 (1): 213. Epub Mar 27. doi: 10.1186/s13071-018-2802-z. more

  • Torelli F, Zander S, Ellerbrok H, Kochs G, Ulrich RG, Klotz C, Seeber F (2018): Recombinant IFN-γ from the bank vole Myodes glareolus: a novel tool for research on rodent reservoirs of zoonotic pathogens
    Sci. Rep. 8 (1): 2797. Epub Feb 12. doi: 10.1038/s41598-018-21143-0. more

  • Klotz C, Šoba B et al. (2017): A European network for food-borne parasites (Euro-FBP): meeting report on 'Analytical methods for food-borne parasites in human and veterinary diagnostics and in food matrices'
    Parasit. Vectors 10 (1): 559. Epub Nov 9. doi: 10.1186/s13071-017-2506-9. more

  • Kraft MR, Klotz C, Bücker R, Schulzke JD, Aebischer T (2017): Giardia's Epithelial Cell Interaction In Vitro: Mimicking Asymptomatic Infection?
    Front. Cell. Infect. Microbiol. 7: 421. Epub Sep 26. doi: 10.3389/fcimb.2017.00421. more

  • Ehret T, Torelli F, Klotz C, Pedersen AB, Seeber F (2017): Translational rodent models for research on parasitic protozoa – a review of confounders and possibilities
    Front. Cell. Infect. Microbiol. 7: 238. Epub Jun 7. doi: 10.3389/fcimb.2017.00238. more

  • Radunovic M, Klotz C, Saghaug CS, Brattbakk HR, Aebischer T et al. (2017): Genetic variation in potential Giardia vaccine candidates cyst wall protein 2 and α1-giardin
    Parasitol. Res. 116 (8): 2151-2158. Epub Jun 3. doi: 10.1007/s00436-017-5516-9. more

  • Helmy YA, Klotz C, Wilking H, Krücken J, Nöckler K, Von Samson-Himmelstjerna G, Zessin KH, Aebischer T (2014): Epidemiology of Giardia duodenalis infection in ruminant livestock and children in the Ismailia province of Egypt: insights by genetic characterization
    Parasit. Vectors 7 (1): 321. Epub Jul 11. doi: 10.1186/1756-3305-7-321. more

  • Obendorf J, Renner Viveros P, Fehlings M, Klotz C, Aebischer T, Ignatius R (2013): Increased expression of CD25, CD83, and CD86, and secretion of IL-12, IL-23, and IL-10 by human dendritic cells incubated in the presence of Toll-like receptor 2 ligands and Giardia duodenalis
    Parasites & Vectors 6 (1): 317. Epub Nov 4. doi: 10.1186/1756-3305-6-317. more

  • Hahn J, Seeber F, Kolodziej H, Ignatius R, Laue M, Aebischer T, Klotz C (2013): High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro
    PLoS One 8 (8): e71597. Epub Aug 19. doi: 10.1371/journal.pone.0071597. more

  • Banik S, Renner Viveros P, Seeber F, Klotz C, Ignatius R, Aebischer T (2013): Giardia duodenalis arginine deiminase modulates the phenotype and cytokine secretion of human dendritic cells by depletion of arginine and formation of ammonia
    Infect. Immun. 81 (7): 2309-2317. Epub Apr 15. doi: 10.1128/IAI.00004-13. more

  • Klotz C, Aebischer T, Seeber F (2012): Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host–parasite interaction
    Int. J. Med. Microbiol. 302 (4-5): 203-209. Epub Aug 13. DOI: 10.1016/j.ijmm.2012.07.010. more

  • Ignatius R, Gahutu JB, Klotz C, Steininger C, Shyirambere C, Lyng M, Musemakweri A, Aebischer T et al. (2012): High Prevalence of Giardia duodenalis Assemblage B Infection and Association with Underweight in Rwandan Children
    PLoS Negl. Trop. Dis. 6 (6): e1677. Epub Jun 12. doi: 10.1371/journal.pntd.0001677. more