Strongyloides ratti: In Vitro and In Vivo Activity of Tribendimidine

Keiser, Jennifer; Kai, Thiemann; Endriss, Yvette; Utzinger, Jürg

doi:10.1371/journal.pntd.0000136

Cited by 32 publications

(24 citation statements)

References 24 publications

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“…For comparison, a complete elimination of adult worms was achieved with ivermectin (0.5 mg/kg) in S. ratti -infected rats [32]. Strongyloides ratti has a remote homolog of DES-2 and ACR-23/MPTL-1 only, which is not targeted by monepantel [22].…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

2011

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BackgroundFew effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases.MethodologyA motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum- or N. americanus-infected hamsters, T. muris- or Ascaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs.Principal FindingsMonepantel showed excellent activity on A. ceylanicum adults (IC50 = 1.7 µg/ml), a moderate effect on T. muris L3 (IC50 = 78.7 µg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC50 = 1.6 and 33.1 µg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively.Conclusions/SignificanceMonepantel reveals low or no activities against N. americanus, T. muris, S. ratti and A. suum in vivo, hence does not qualify as drug development candidate for human soil-transmitted helminthiases.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

2011

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“…C aenorhabditis elegans and P. pacificus were grown on nematode growth medium (NGM) plates with a lawn of Escherichia coli strain OP50 (Brenner 1974). The S. ratti animals were maintained using Wistar rats by serial passage as described previously (Viney and Lok 2007; Keiser et al . 2008).…”

Section: Methodsmentioning

confidence: 99%

Conserved miRNAs Are Candidate Post-Transcriptional Regulators of Developmental Arrest in Free-Living and Parasitic Nematodes

Ahmed

Chang

Younis

et al. 2013

Genome Biology and Evolution

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Animal development is complex yet surprisingly robust. Animals may develop alternative phenotypes conditional on environmental changes. Under unfavorable conditions, Caenorhabditis elegans larvae enter the dauer stage, a developmentally arrested, long-lived, and stress-resistant state. Dauer larvae of free-living nematodes and infective larvae of parasitic nematodes share many traits including a conserved endocrine signaling module (DA/DAF-12), which is essential for the formation of dauer and infective larvae. We speculated that conserved post-transcriptional regulatory mechanism might also be involved in executing the dauer and infective larvae fate. We used an unbiased sequencing strategy to characterize the microRNA (miRNA) gene complement in C. elegans, Pristionchus pacificus, and Strongyloides ratti. Our study raised the number of described miRNA genes to 257 for C. elegans, tripled the known gene set for P. pacificus to 362 miRNAs, and is the first to describe miRNAs in a Strongyloides parasite. Moreover, we found a limited core set of 24 conserved miRNA families in all three species. Interestingly, our estimated expression fold changes between dauer versus nondauer stages and infective larvae versus free-living stages reveal that despite the speed of miRNA gene set evolution in nematodes, homologous gene families with conserved “dauer-infective” expression signatures are present. These findings suggest that common post-transcriptional regulatory mechanisms are at work and that the same miRNA families play important roles in developmental arrest and long-term survival in free-living and parasitic nematodes.

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“…The experimental protocols have been reviewed and confirmed by the responsible federal health authorities of the State of Hamburg (Hamburg, Behoerde fuer Gesundheit und Verbraucherschutz: permission number 89/09). Four to 6-week-old Wistar rats (Rattus norvegicus) from Charles River were used to maintain the cycle by serial passage as described (Keiser, Thiemann, Endriss, & Utzinger, 2008;Viney & Lok, 2007). For the collection of different stages, standard methods were used which were established in our laboratory Younis et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

Identification, isolation, and cloning of the full-length sequence of a gene encoding trypsin inhibitor-like protein (TIL) secreted by the intestinal parasitic nematode Strongyloides ratti

Younis

Brattig

2018

JoBAZ

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Background: Intestinal nematodes may interact with the intestinal mucosal host cells through molecules they produced actively in the host environment. Many excretory/secretory products (ESP) of the intestinal nematodes are considered as interesting candidates to be examined in vitro on their tolerance-inducing activities. Nematode-derived protease inhibitors are believed to have multiple, specific abilities for the host immunomodulation, playing on various immune effector mechanisms. Among the previously identified 500 ESP from Strongyloides ratti, trypsin inhibitor-like (Sra-TIL) peptides were detected in high concentration in the ESP of the parasitic female (pF). The aim is to identify interesting tolerance-inducing proteins belonging to the longtime adapted human biome which may be potentially applied to moderate inflammatory immune reactions.

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Strongyloides ratti: In Vitro and In Vivo Activity of Tribendimidine

Cited by 32 publications

References 24 publications

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

Conserved miRNAs Are Candidate Post-Transcriptional Regulators of Developmental Arrest in Free-Living and Parasitic Nematodes

Identification, isolation, and cloning of the full-length sequence of a gene encoding trypsin inhibitor-like protein (TIL) secreted by the intestinal parasitic nematode Strongyloides ratti

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