Abstract:The protozoan parasite Histomonas meleagridis is a member of the family Monocercomonadidae in the class Trichomonada. Due to food safety concerns, currently no prophylactic or therapeutic drug against the parasite is licensed in the European Union. Benzimidazoles are antiparasitic drugs, and some of them are licensed for use in food-producing animals. Benzimidazoles act on beta-tubulin, and the beta-tubulin sequence allows predictions about the efficacy of benzimidazoles. In this study, we sequenced and analyz… Show more
“…Literature on trichomonads such as Tritrichomonas foetus and free-living Monocercomonas species (166)(167)(168), all of which are parabasalids that share an ancestor with D. fragilis (169), shows that these species produce pseudocysts under unfavorable environmental conditions. Pseudocysts are nonmotile, multinucleated, typically spherical forms without a true cyst wall.…”
SUMMARYDientamoeba fragilisis a protozoan parasite of the human bowel, commonly reported throughout the world in association with gastrointestinal symptoms. Despite its initial discovery over 100 years ago, arguably, we know less about this peculiar organism than any other pathogenic or potentially pathogenic protozoan that infects humans. The details of its life cycle and mode of transmission are not completely known, and its potential as a human pathogen is debated within the scientific community. Recently, several major advances have been made with respect to this organism's life cycle and molecular biology. While many questions remain unanswered, these and other recent advances have given rise to some intriguing new leads, which will pave the way for future research. This review encompasses a large body of knowledge generated on various aspects ofD. fragilisover the last century, together with an update on the most recent developments. This includes an update on the latest diagnostic techniques and treatments, the clinical aspects of dientamoebiasis, the development of an animal model, the description of aD. fragiliscyst stage, and the sequencing of the firstD. fragilistranscriptome.
“…Literature on trichomonads such as Tritrichomonas foetus and free-living Monocercomonas species (166)(167)(168), all of which are parabasalids that share an ancestor with D. fragilis (169), shows that these species produce pseudocysts under unfavorable environmental conditions. Pseudocysts are nonmotile, multinucleated, typically spherical forms without a true cyst wall.…”
SUMMARYDientamoeba fragilisis a protozoan parasite of the human bowel, commonly reported throughout the world in association with gastrointestinal symptoms. Despite its initial discovery over 100 years ago, arguably, we know less about this peculiar organism than any other pathogenic or potentially pathogenic protozoan that infects humans. The details of its life cycle and mode of transmission are not completely known, and its potential as a human pathogen is debated within the scientific community. Recently, several major advances have been made with respect to this organism's life cycle and molecular biology. While many questions remain unanswered, these and other recent advances have given rise to some intriguing new leads, which will pave the way for future research. This review encompasses a large body of knowledge generated on various aspects ofD. fragilisover the last century, together with an update on the most recent developments. This includes an update on the latest diagnostic techniques and treatments, the clinical aspects of dientamoebiasis, the development of an animal model, the description of aD. fragiliscyst stage, and the sequencing of the firstD. fragilistranscriptome.
“…and Ascaris sp – data not shown) and the implications of this are that the amino acids predictive for albendazole susceptibility are moved forward by one additional position (see Fig. 1), compared to previous reports describing beta-tubulin sequences [16, 21]. Figure 1.Full alignment of beta-tubulin amino acid sequences from D. fragilis with tubulin sequences derived from Trichomonads and other eukaryotes.…”
Section: Resultsmentioning
confidence: 81%
“…Subsequently, susceptibility of benzimidazoles was shown for G. intestinalis and microsporidia [21]. More recently, the activity of benzimidazoles was tested against H. meleagridis and they were shown to be an ineffective agent for treatment in vitro [16]. Resistance to the benzimidazoles has been observed in parasitic nematodes of livestock animals since the early 1960s [11].…”
Section: Discussionmentioning
confidence: 99%
“…Concentrations ranging from 2 μg/mL to 500 μg/mL resulted in D. fragilis trophozoite cell counts similar to that of the control. Although both Giardia and Trichomonas have been shown to be susceptible to benzimidazoles, the closely related H. meleagridis was shown to be resistant to benzimidazoles [9, 16, 17]. The exact mechanism for resistance is however unknown [16].…”
Section: Discussionmentioning
confidence: 99%
“…In Trichomonad parasites, agreement between beta-tubulin sequences and susceptibility to benzimidazoles in vitro has been established for T. vaginalis [20, 21]. However, a study on H. meleagridis found that while histomonal amino acid sequences predicted a susceptibility to benzimidazoles, no correlation was found with in vitro activity for these agents [16]. …”
Recently, Dientamoeba fragilis has emerged as a significant and common enteropathogen. The majority of patients with dientamoebiasis present with gastrointestinal complaints and chronic symptoms are common. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Despite this, there is very little in vitro susceptibility data available for the organism. Benzimidazoles are a class of antiparasitic drugs that are commonly used for the treatment of protozoan and helminthic infections. Susceptibility testing was undertaken on four D. fragilis clinical isolates against the following benzimidazoles: albendazole, flubendazole, mebendazole, nocodazole, triclabendazole and thiabendazole. The activities of the antiprotozoal compounds at concentrations ranging from 2 μg/mL to 500 μg/mL were determined via cell counts of D. fragilis grown in xenic culture. All tested drugs showed no efficacy. The beta-tubulin transcript was sequenced from two of the D. fragilis isolates and amino acid sequences predicted a susceptibility to benzimidazoles. This is the first study to report susceptibility profiles for benzimidazoles against D. fragilis, all of which were not active against the organism. This study also found that beta-tubulin sequences cannot be used as a reliable marker for resistance of benzimidazoles in D. fragilis.
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