Glutathione S-transferase (GST) in ticks

Principal investigators: Dr. Georg Duscher, Adnan Hodzic.

Technical development: Walpurga Wille-Piazzai, Roman Peschke.

Abstract: GSTs are enzymes responsible for the detoxification of cells of many animal species. In some arthropod species it seems to be relevant for persistence against pesticides. We investigate tick species for the occurrence of their GSTs as well as the role of these GSTs during detoxification. Therefore we challenge the ticks with acaricides e.g. permethrin, and try to find differences in the expression levels of GSTs. By blocking of gst-gene one by one, we aim to completely block the detoxification of ticks, rendering them susceptible for acaricides. Additionally by silencing the detoxification of the tick cells, it also might hamper the exclusion of xeniobiotic compounds of the blood meal such as haemoglobin. Consequently poisoning of ticks due to up-taken blood meal could be possible. By elucidating the different GST and their gst genes, concealed vaccine targets could be identified.

Ticks im Kosovo

Principal investigators: Prof. Anja Joachim, Dr. Georg Duscher in collaboration with Kurtesh Sherifi, University of Prishtina, HigherKos

Abstract: The information on ticks and tick-borne pathogens in Prishtina is scarce. In the past years human cases of Crimean-Congo-Haemorrhagic-Fever (CCHF) were reported, but data on the vector tick Hyalomma sp. are lacking. Knowledge about tick fauna and abundance is restricted. Even more there are hardly any data on borrelia or TBE. Therefore sampling of ticks of several region of Kosovo is conducted. Thereafter DNA/RNA extraction are made and screened for CCHF, TBE and Borrelia sp. by using commercial kits.

Mimotopes as targets for pathogenic aquaporin 4-specific autoantibodies in neuromyelitis optica

Principal investigator: Dr. Monika Bradl (Medical University Vienna), Dr. Georg Duscher

Abstract: Neuromyelitis optica (NMO) is an acute inflammatory demyelinating disease of the central nervous system (CNS). Hallmark of this disease are astrocytopathic lesions in spinal cord and optic nerves, and the presence of so-called NMO-IgG in the vast majority of patients. NMO-IgG are antibodies directed against the water channel aquaporin 4 (AQP4). These antibodies are not only a diagnostic marker of NMO, but they are pathogenic. Unfortunately, the triggers for the production of pathogenic NMO-IgG or for the increase in AQP4-specific antibodies in established NMO remain essentially unknown. Similarly, we do not yet have any biomarkers available, which could reveal the size and quality of the AQP4-specific antibody repertoire in patients, or help to predict disease course, severity or treatment responses. The pathogenic AQP4-specific antibodies of NMO patients recognize conformational epitopes formed by extracellular loops of AQP4. However, antibodies specific for conformational epitopes can also recognize linear peptides mimicking these epitopes (= mimotopes). Therefore, the identification of linear peptides binding to AQP4-specific antibodies of NMO patients could help us to specifically address the open issues: If such linear peptides are found in naturally occurring antigens to which NMO patients could have been exposed, these antigens might play a role in the formation and/or expansion of AQP4-specific antibodies in NMO; if they are not found in these sources, but cross-react with AQP4-specific antibodies simply due to structural similarity of a random amino acid sequence to the conformational epitope, such mimotopes could represent ideal tools to identify subsets of AQP4-specific antibodies, and to probe the AQP4-specific antibody repertoire of individual patients. In the current proposal, we plan to continue our mimotope search for NMO-IgGs, to apply them to study the AQP4-specific antibody repertoire of patients, and to analyze whether there are dominating anti-AQP4-reactivities in NMO patients, and whether patients with specific mimotope-binding patterns of their AQP4-antibody repertoire differ from each other, e.g. in terms of disease severity, titers, or treatment responses.

Wild canids as reservoirs for ticks and tick-borne pathogens in Central and Eastern Europe

Principal investigators: Dr. Georg Duscher, Adnan Hodzic.

Abstract: Central European wild canids (e.g. red foxes, golden jackals, wolves, raccoon dogs) are important hosts of ixodid ticks and recently they have been recognized as potential reservoirs of several tick-borne pathogens of medical and veterinary concern. Species like the red fox (Vulpes vulpes) and the golden jackal (Canis aureus) also represent an important source of infections for domestic animals and humans, mostly due to their close proximity to human settlements and frequent exposure to different vector species. Currently, both species have rapidly growing populations in urban and periurban areas, and they and the ticks they carry are spreading their ranges from southern parts toward Central and Eastern Europe, increasing the risk of human and domestic animal exposure to ticks and the pathogens they transmit. Therefore, the project is focused on prevalence and geographical distribution of tick-borne pathogens (e.g. Babesia sp., Hepatozoon canis, Anaplasmataceae, Rickettsia sp.) in wild canids and ticks from Central and Eastern Europe and the determination of risk factors for human infections. Moreover, we investigate the genetic diversity of tick-borne pathogens related to vector, host species, geographical region, season and influence of enviromental factors on their prevalence and distribution.