echinococcus multilocularis
Recently Published Documents


TOTAL DOCUMENTS

980
(FIVE YEARS 169)

H-INDEX

51
(FIVE YEARS 5)

2022 ◽  
Vol 16 (1) ◽  
pp. e0009192
Author(s):  
Michael Weingartner ◽  
Simon Stücheli ◽  
Fadi Jebbawi ◽  
Bruno Gottstein ◽  
Guido Beldi ◽  
...  

Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. Results E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. Conclusions and significance AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.


2022 ◽  
Vol 164 (1) ◽  
pp. 71-78
Author(s):  
C. F. Frey ◽  
W.U. Basso ◽  
S. Zürcher-Giovannini ◽  
I. Marti ◽  
S. Borel ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
pp. 4
Author(s):  
Xuedong He ◽  
Jing Zhang ◽  
Yue Sun ◽  
Tianyan Lan ◽  
Xiaola Guo ◽  
...  

Glycolysis is one of the important ways by which Echinococcus multilocularis acquires energy. Fructose-1, 6-bisphosphate aldolase (FBA) plays an important role in this process, but it is not fully characterized in E. multilocularis yet. The results of genome-wide analysis showed that the Echinococcus species contained four fba genes (FBA1-4), all of which had the domain of FBA I and multiple conserved active sites. EmFBA1 was mainly located in the germinal layer and the posterior of the protoscolex. The enzyme activity of EmFBA1 was 67.42 U/mg with Km and Vmax of 1.75 mM and 0.5 mmol/min, respectively. EmFBA1 was only susceptible to Fe3+ but not to the other four ions (Na+, Ca2+, K+, Mg2+), and its enzyme activity was remarkably lost in the presence of 0.5 mM Fe3+. The current study reveals the biochemical characters of EmFBA1 and is informative for further investigation of its role in the glycolysis in E. multilocularis.


2021 ◽  
Vol 15 (12) ◽  
pp. e0010027
Author(s):  
Kristin Stoll ◽  
Monika Bergmann ◽  
Markus Spiliotis ◽  
Klaus Brehm

Background The metacestode larval stage of the fox-tapeworm Echinococcus multilocularis causes alveolar echinococcosis by tumour-like growth within the liver of the intermediate host. Metacestode growth and development is stimulated by host-derived cytokines such as insulin, fibroblast growth factor, and epidermal growth factor via activation of cognate receptor tyrosine kinases expressed by the parasite. Little is known, however, concerning signal transmission to the parasite nucleus and cross-reaction with other parasite signalling systems. Methodology/Principal findings Using bioinformatic approaches, cloning, and yeast two-hybrid analyses we identified a novel mitogen-activated kinase (MAPK) cascade module that consists of E. multilocularis orthologs of the tyrosine kinase receptor interactor Growth factor receptor-bound 2, EmGrb2, the MAPK kinase kinase EmMEKK1, a novel MAPK kinase, EmMKK3, and a close homolog to c-Jun N-terminal kinase (JNK), EmMPK3. Whole mount in situ hybridization analyses indicated that EmMEKK1 and EmMPK3 are both expressed in E. multilocularis germinative (stem) cells but also in differentiated or differentiating cells. Treatment with the known JNK inhibitor SP600125 led to a significantly reduced formation of metacestode vesicles from stem cells and to a specific reduction of proliferating stem cells in mature metacestode vesicles. Conclusions/Significance We provide evidence for the expression of a MEKK1-JNK MAPK cascade module which, in mammals, is crucially involved in stress responses, cytoskeletal rearrangements, and apoptosis, in E. multilocularis stem cells. Inhibitor studies indicate an important role of JNK signalling in E. multilocularis stem cell survival and/or maintenance. Our data are relevant for molecular and cellular studies into crosstalk signalling mechanisms that govern Echinococcus stem cell function and introduce the JNK signalling cascade as a possible target of chemotherapeutics against echinococcosis.


2021 ◽  
Author(s):  
Isabelle Kwiedor ◽  
Wolfgang Kratzer ◽  
Patrycja Schlingeloff ◽  
Julian Schmidberger

Zusammenfassung Ziel der Studie Die alveoläre Echinokokkose (AE) ist eine seltene Parasitose verursacht durch den Erreger Echinococcus multilocularis. In vielen Ländern wird ein Anstieg der Fallzahlen beobachtet. Ziel der Arbeit ist die Untersuchung der aktuellen Prävalenz und der Veränderung des geographische Verteilungsmusters. Methodik Die Datenerhebung erfolgte retrospektiv für den Zeitraum 1992–2018 anhand der registrierten Fälle im nationalen Erkrankungsregistern für die AE in Deutschland. Die statistische Analyse erfolgte mittels dem statistischen Auswertungssystem SAS Version 9.4 (SAS Institute, Cary, N.C., USA). Ergebnisse Das Untersuchungskollektiv von n=569 Patienten umfasste n=322 (56,59%) Frauen und n=247 (43,40%) Männer. Das mittleres Durchschnittsalter der Patienten mit alveolärer Echinokokkose bei Erstvorstellung betrug 53,90±17,54 Jahre (Median: 56,00 Jahre). Die Moran’s I Teststatistik ergab für den Zeitraum 1992–2018 eine positive räumliche Autokorrelation entsprechend einer heterogenen Verteilung der Erkrankungsfälle in Deutschland (I=0,4165; Z=10,9591, p=0,001). Für den gesamten Untersuchungszeitraum (1992–2018) konnte ein Anstieg der alters- und geschlechtsspezifischen Prävalenz ermittelt werden. Die Gesamtprävalenz im Zeitraum 1992–2018 lag bei 0,71 Erkrankungsfälle pro 100 000 Einwohner. Die Ermittlung der Prävalenz für den Zeitraum 1992–2018 ergab für Männern 0,31 Fälle, für Frauen 0,40 Fälle pro 100 000 Einwohner. Im Zeitraum von 1992–1996 waren in 11/16 (68,8%) Bundesländern (Berlin, Brandenburg, Bremen, Hamburg, Mecklenburg-Vorpommern, Rheinland-Pfalz, Saarland, Sachsen, Sachsen-Anhalt, Schleswig-Holstein und Thüringen) noch keine AE-Fälle registriert worden. Die Auswertung zeigt jüngst ein vermehrtes vorkommen von Fällen in den Bundesländern Hessen, Rheinland-Pfalz und Nordrhein-Westfalen. Schlussfolgerungen Die Analyse zeigt einen Anstieg der Prävalenz sowie zunehmend vermehrt Erkrankungsfälle außerhalb der klassischen Hauptendemiegebiete Baden-Württemberg und Bayern.


2021 ◽  
pp. 102522
Author(s):  
Izumi Kida ◽  
Hirokazu Kouguchi ◽  
Takao Irie ◽  
Kinpei Yagi ◽  
Ryo Nakao ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Deping Cao ◽  
Emad Shamsan ◽  
Bofan Jiang ◽  
Haining Fan ◽  
Yaogang Zhang ◽  
...  

Abstract Background Echinococcus multilocularis is the causative agent of human hepatic alveolar echinococcosis (AE). AE can cause damage to several organs, primarily the liver, and have severe outcomes, such as hepatic failure and encephalopathy. The main purpose of this study was to explore the interactions between hepatic stellate cells (HSCs) and E. multilocularis protoscoleces (PSCs). The results of this study provide an experimental basis for further examination of the pathogenesis of hepatic fibrosis due to AE infection. Methods We investigated the role of Echinococcus multilocularis (Echinococcus genus) PSCs in hepatic fibrosis by examining structural changes and measuring hepatic fibrosis-related protein levels in cocultures of PSCs and human HSCs. Structural changes were detected by transmission electron microscopy (TEM), and levels of the hepatic fibrosis-related proteins collagen I (Col-I), alpha-smooth muscle actin (α-SMA) and osteopontin (OPN) were measured by western blotting and enzyme-linked immunosorbent assay (ELISA). Results Under coculture (1) both PSCs and HSCs exhibited morphological changes, as observed by TEM; (2) Col-I, α-SMA, and OPN expression levels, which were determined by western blotting and ELISA, significantly increased after 3 days of incubation. Conclusions The results of this study provide insights into the molecular mechanisms of AE-induced hepatic fibrosis. Graphical abstract


2021 ◽  
Vol Volume 14 ◽  
pp. 5651-5660
Author(s):  
Fengming Tian ◽  
Tao Jiang ◽  
Xinwei Qi ◽  
Zhenyu Zhao ◽  
Bin Li ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document