The role of evolutionarily conserved signalling systems in Echinococcus multilocularis development and host–parasite interaction

Abstract

Alveolar echinococcosis, one of the most serious and life-threatening zoonoses in the world, is caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis. Mostly due to its accessibility to in vitro cultivation, this parasite has recently evolved into an experimental model system to study larval cestode development and associated host-parasite interaction mechanisms. Respective advances include the establishment of axenic in vitro cultivation systems for parasite larvae as well as culture systems by which the early development of metacestode vesicles from totipotent parasite stem cells can be reconstituted under controlled laboratory conditions. A series of evolutionarily conserved signalling molecules of the insulin, epidermal growth factor and transforming growth factor-beta pathways that are able to functionally interact with corresponding host cytokines have been described in E. multilocularis and most likely play a crucial role in parasite development within the liver of the intermediate host. Furthermore, a whole genome sequencing project has been initiated by which a comprehensive picture on E. multilocularis cell-cell communication systems will be available in due time, including information on parasite cytokines that are secreted towards host tissue and thus might affect the immune response. In this article, an overview of our current picture on Echinococcus signalling systems will be given, and the potential to exploit these pathways as targets for anti-parasitic chemotherapy will be discussed.

Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice

“…Meanwhile, several host-derived molecules were previously reported to exist in the cyst fluid or on the wall (Kassis and Tanner, 1977;Ali-Khan and Siboo, 1981), indicating that certain host-derived factors are transported through the laminated layer and are involved in parasite development in the hosts. In recent years, great progress has been made in elucidating the mechanisms of parasite development in the hosts by identifying the evolutionarily conserved signaling systems in E. multilocularis, which can interact with hostderived molecules (Konrad et al, 2003;Spiliotis et al, 2003Spiliotis et al, , 2005Spiliotis et al, , 2006Zavala-Góngora et al, 2003Gelmedin et al, 2008Gelmedin et al, , 2010Brehm, 2010;Förster et al, 2011). Specifically, interactions between parasite receptors and host-derived molecules, such as epidermal growth factor and insulin have been demonstrated experimentally (Spiliotis et al, 2006;Gelmedin et al, 2008;Brehm, 2010), strongly suggesting that parasite development is triggered by host signaling systems.…”

Recent publications in medical microbiology and immunology: a retrospective

“…Molecular pathways to pathogen variation and adaptation to the host have been reviewed for E. coli [46] (16), Bordetella [47], and Neisseria [48,49]. Of related interest are the regulation of white-opaque switch in Candida albicans [50] and the role of evolutionary conserved signaling systems in Echinococcus with regard to host-parasite interaction [51].…”

In vitro efficacy of the anticancer drug imatinib on Echinococcus multilocularis larvae

“…The metacestode larval stage of the fox tapeworm (Echinococcus multilocularis) is the causative agent of alveolar echinococcosis (AE), one of the most serious parasitic infections in humans [1,2]. Infection of the intermediate host is initiated by oral uptake of the oncosphere, which subsequently undergoes a metamorphosis towards the metacestode within the host liver [2].…”

“…Infection of the intermediate host is initiated by oral uptake of the oncosphere, which subsequently undergoes a metamorphosis towards the metacestode within the host liver [2]. Following asexual proliferation of metacestode tissue within the intermediate host's organs in an infiltrative, tumour-like manner, protoscoleces are formed as the larval stage that is eventually transmitted to the definitive host [2]. Chemotherapeutic anti-AE treatment options are currently very limited and rely on benzimidazoles (BZs) that target parasite ␤-tubulin [1].…”

“…Despite some reports on antiEchinococcus activities of other compounds, such as amphotericin B, isoflavones or nitazoxanide [1], no reliable chemotherapeutic alternative has yet been developed, underscoring the need to identify novel drug targets and inhibitory drugs against AE. Cellular signalling components have already been suggested as promising targets in anthelminthic chemotherapy owing to their crucial participation in regulating development and proliferation of metazoans, including parasitic helminths [2,4]. Furthermore, owing to their important role in cancerogenesis, the biochemistry of respective signalling molecules such as kinases and phosphatases is very well studied, and a broad range of inhibitory compounds is available.…”