EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Amahong, Kuerbannisha; Yan, Mingzhi; Li, Jintian; Yang, Ning; Liu, Hui; Bi, Xiaojuan; Vuitton, Dominique A.; Lin, Renyong; Lü, Guodong

doi:10.3389/fcimb.2021.747739

Cited by 6 publications

(6 citation statements)

References 69 publications

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“…In experimentally infected mice, a 10 mg/kg dose of WZB117 exhibited significant reduction of number and size of hydatid cysts as efficiently as albendazole. In addition, no change was observed in either body weight or blood glucose level in the treated mice for 4 weeks [65] .…”

Section: Cytochrome C Complex (Cyt C)mentioning

confidence: 86%

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Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part III: Helminths

Abaza

2022

Parasitologists United Journal

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The term "magic bullet" was chosen to explain how a drug kills the pathogen with a greater affinity and specificity to its target without effecting its orthologue in human. The ideal parasite target is a molecule essential for its viability, growth, proliferation, and differentiation. The majority of commonly administered anthelminthics target either neuromuscular elements, or metabolic pathways. On the other hand, genomics studies combined with transcriptome analyses revealed advanced information in understanding hostparasite interactions that yielded clues for new strategies in identification of new parasite targets and designing novel inhibitors. In fact, next generation sequencing technology provides unique opportunities to understand parasites molecular biology and their role in parasite-host interactions. Besides, drug repurposing is a promising approach to expand the pool of molecules with potent inhibitory activity against a specific parasite target. The present review aims to highlight the proposed potential helminth drug targets with special emphasis on the major tropical diseases such as schistosomiasis, hydatid cyst, lymphatic filariasis, onchocerciases and soil transmitted diseases. The review also highlights hypothesized potential targets for future development of novel anthelminthics utilizing aminoacyl-tRNA synthetase and the 20S core proteasome, as well as new strategies targeting parasitic response to overcome host mechanistic target of rapamycin.

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Section: Cytochrome C Complex (Cyt C)mentioning

confidence: 86%

“…Transporters: Recently, Amahong et al [65] proposed glucose transporter 1 (GLUT1), responsible for the transmembrane transport of glucose, a promising drug target in E. granulosus. They cloned EgGLUT1 encoding gene from E. granulosus sensu stricto and observed its essentiality for glucose uptake and protoscoleces viability.…”

Section: Cytochrome C Complex (Cyt C)mentioning

confidence: 99%

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part III: Helminths

Abaza

2022

Parasitologists United Journal

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“…ABZ and HM (both 120 μM) were used as positive controls, and the viability of PSCs was detected by a 1% eosin staining assay after 48 h of in vitro treatment (PSCs that turned red after eosin staining were considered dead while surviving PSCs were colorless). 19 Each experiment was repeated at least three times. PSCs were collected for observation by scanning electron microscopy (SEM) (LEO1430VP, LEO company, Germany) after drug intervention, and the experiments were performed as previously described.…”

Section: Methodsmentioning

confidence: 99%

“… 23 Randomly selected treated mouse cysts were observed by transmission electron microscopy (TEM) (JEM1230, JEOL company, Japan) as described previously. 19 …”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis

Chen,

Yan,

Gao

et al. 2023

DDDT

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Introduction Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato ( s.l .) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs. Methods In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto ( s.s .) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study. Results These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 μM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s ., which may be the mechanism by which these drugs produce their therapeutic effects. Discussion Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.

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“…Surgery and anti-helminthic drugs are the treatment of choice for AE (3). Some proteins of E. multilocularis with high immunogenicity could induce immune responses to prevent infection (4)(5)(6)(7). Our previous study has shown that vaccination with dominant epitopes, such as EMY162, Glut1, TSP3, 14-3-3 and EM-LAP, could significantly decrease the number and size of cysts in a mouse model infected with E. Multilocularis metacestodes.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

Zhou

et al. 2022

Front. Immunol.

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Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.

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EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Cited by 6 publications

References 69 publications

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part III: Helminths

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part III: Helminths

In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

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