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Purpose of Review: Giardia lamblia is a common intestinal parasite worldwide, mainly in children from low- and middle-income countries (LMIC). Also, it has been associated with increased intestinal permeability, stunting, and cognitive impairment. Nonetheless, the pathogenesis of long-term consequences is difficult to elucidate. Recent Findings: Recent studies try to understand the long-term consequences of Giardia infections. First, well-characterized studies associate Giardia with intestinal damage and child growth. Second, infections appear not to be associated with inflammation, but "lack of inflammation" may not, however, entirely exclude a pro-inflammatory pathway. Finally, some important amino acids are lower and could contribute to prolongate stunting and cognitive deficit. Summary: Giardia infections in LMIC used to be associated with child growth shortfalls, gut permeability, and cognitive deficits. Multifactorial effects could be associated with Giardia, including nutritional, altered microbiota, and generation of potentially toxic microbial metabolic byproducts, all together increasing risk of long-term outcomes.

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Histone post-translational modifications are extensively studied for their role in regulating gene transcription and cellular environmental adaptation. Research into these modifications has recently begun in the protozoan parasite Giardia lamblia, focusing on histone-modifying enzymes and specific post-translational changes. In the transformation from the trophozoite to the cyst form in the life cycle of this parasite, significant morphological and genetic alterations occur, culminating in the synthesis of cyst wall proteins responsible for forming the protective cyst wall. It has been previously demonstrated that histone deacetylation is required during encystation and that the enzyme lysine methyltransferase 1 is involved in the upregulation of encystation. Our study aims to extend the analysis to lysine methyltransferase 2 (GlKMT2) function. For this, two constructs were generated: one that downregulate the expression of GLKMT2 via antisense (glkmt2-as transgenic cells) and the other overexpressing GlKMT2 (glkmt2-ha transgenic cells). We found that the glktm2-as transgenic cells showed an arrest in progress at the late encystation stage. Consequently, the number of cysts produced was lower than that of the control cells. On the other hand, we found that the overexpression of GlKMT2 acts as a negative mutant of the enzyme. In this way, these glktm2-ha transgenic cells showed the same behavior during growth and encystation as glkmt2-as transgenic cells. This interplay between different enzymes acting during encystation reveals the complex process behind the differentiation of the parasite. Understanding how these enzymes play their role during the encystation of the parasite would allow the design of inhibitors to control the parasite.

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Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.

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Giardiasis is a parasitosis caused by Giardia lamblia with significant epidemiological and clinical importance due to its high prevalence and pathogenicity. The lack of optimal therapies for treating this parasite makes the development of new effective chemical entities an urgent need. In the search for new inhibitors of the adenylyl cyclase gNC1 obtained from G. lamblia, 14 extracts from Argentinian native plants were screened. Lepechinia floribunda and L. meyenii extracts exhibited the highest gNC1 inhibitory activity, with IC50 values of 9 and 31 µg/mL, respectively. In silico studies showed rosmarinic acid, a hydroxycinnamic acid present in both mentioned species, to be a promising anti-gNC1 compound. This result was confirmed experimentally, with rosmarinic acid showing an IC50 value of 10.1 µM. Theoretical and experimental findings elucidate the molecular-level mechanism of rosmarinic acid, pinpointing the key interactions stabilizing the compound-enzyme complex and the binding site. These results strongly support that rosmarinic acid is a promising scaffold for developing novel compounds with inhibitory activity against gNC1, which could serve as potential therapeutic agents to treat giardiasis.

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The inner structure of the flagella of Giardia intestinalis is similar to that of other organisms, consisting of nine pairs of outer microtubules and a central pair containing radial spokes. Although the 9+2 axonemal structure is conserved, it is not clear whether subregions, including the transition zone, are present in the flagella of this parasite. Giardia axonemes originate from basal bodies and have a lengthy cytosolic portion before becoming active flagella. The region of the emergence of the flagellum is not accompanied by any membrane specialization, as seen in other protozoa. Although Giardia is an intriguing model of study, few works focused on the ultrastructural analysis of the flagella of this parasite. Here, we analyzed the externalization region of the G. intestinalis flagella using ultra-high resolution scanning microscopy (with electrons and ions), atomic force microscopy in liquid medium, freeze fracture, and electron tomography. Our data show that this region possesses a distinctive morphological feature - it extends outward and takes on a ring-like shape. When the plasma membrane is removed, a structure surrounding the axoneme becomes visible in this region. This new extra-axonemal structure is observed in all pairs of flagella of trophozoites and remains attached to the axoneme even when the interconnections between the axonemal microtubules are disrupted. High-resolution scanning electron microscopy provided insights into the arrangement of this structure, contributing to the characterization of the externalization region of the flagella of this parasite.

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Abstract Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of bird's enclousres are suggested to avoid parasites.

RESUMO Amostras de sangue e fezes de perdiz chukar (Alectoris chukar), faisão-albino (Phasianus colchicus), faisão-prateado (Lophura nycthemera), periquito-de-rosa (Psittacula krameri) e perus (Meleagris gallopavo) foram analisadas para verificar a prevalência de parasitas. Para registrar os parasitas, essas cinco espécies de aves foram colocadas em gaiolas separadas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore, Paquistão. Cem amostras fecais e 100 amostras de sangue para cada espécie de ave foram inspecionadas para analisar os parasitas internos. Durante o presente estudo, foram examinadas 17 espécies de endoparasitas, 14 de amostras fecais e 3 de sangue. Foram estudadas duas espécies de ectoparasitas, ou seja, o ácaro Dermanyssus gallinae 42% e o carrapato aviário Args persicus 41%. Os parasitas sanguíneos incluíram Plasmodium juxtanucleare 50%, Leucoctoyzoon simond com prevalência parasitária de 40% e Aegyptinella pullorum com prevalência parasitária de 40%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Allodpa suctoria 2%, Syngamus traqueia com prevalência parasitária de 60%, Capillaria annulata 37,5%, Ascardia galli 24%, Capillaria anatis 40% e Heterakis gallinarum 28,3%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 50% e Prosthogonimus macrorchis 21% também foram documentados em amostras fecais de aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 72% e 3 espécies de protozoários, isto é, Eimeria maxima com prevalência parasitária de 21%, Giardia lamblia 41% e Histomonas meleagridis 18% foram documentadas durante a análise corpológica. Em nossa recomendação, o saneamento adequado, medicação e vacinação de invólucros de pássaros são sugeridos para evitar parasitas.

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Abstract Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of birds enclousres are suggested to avoid parasites.

RESUMO Amostras de sangue e fezes de perdiz chukar (Alectoris chukar), faisão-albino (Phasianus colchicus), faisão-prateado (Lophura nycthemera), periquito-de-rosa (Psittacula krameri) e perus (Meleagris gallopavo) foram analisadas para verificar a prevalência de parasitas. Para registrar os parasitas, essas cinco espécies de aves foram colocadas em gaiolas separadas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore, Paquistão. Cem amostras fecais e 100 amostras de sangue para cada espécie de ave foram inspecionadas para analisar os parasitas internos. Durante o presente estudo, foram examinadas 17 espécies de endoparasitas, 14 de amostras fecais e 3 de sangue. Foram estudadas duas espécies de ectoparasitas, ou seja, o ácaro Dermanyssus gallinae 42% e o carrapato aviário Args persicus 41%. Os parasitas sanguíneos incluíram Plasmodium juxtanucleare 50%, Leucoctoyzoon simond com prevalência parasitária de 40% e Aegyptinella pullorum com prevalência parasitária de 40%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Allodpa suctoria 2%, Syngamus traqueia com prevalência parasitária de 60%, Capillaria annulata 37,5%, Ascardia galli 24%, Capillaria anatis 40% e Heterakis gallinarum 28,3%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 50% e Prosthogonimus macrorchis 21% também foram documentados em amostras fecais de aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 72% e 3 espécies de protozoários, isto é, Eimeria maxima com prevalência parasitária de 21%, Giardia lamblia 41% e Histomonas meleagridis 18% foram documentadas durante a análise corpológica. Em nossa recomendação, o saneamento adequado, medicação e vacinação de invólucros de pássaros são sugeridos para evitar parasitas.

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Anti-Ascaris lumbricoides (Asc) IgE and IgG can immunomodulate the allergy; however, the influence of these isotypes has not been investigated in the giardiasis and allergy. Therefore, the frequency of respiratory allergy (RA) symptoms in Giardia lamblia-infected children, with or without anti-Asc IgE, IgG1, or IgG4 and Th1, Th2/Treg, and Th17 cytokine production, was evaluated. We performed a case-control study with children aged 2-10 years old selected by questionnaire and stool exams to form the groups: infected or uninfected with RA (G-RA, n = 55; nG-RA, n = 43); infected and uninfected without RA (G-nRA, n = 59; nG-nRA, n = 54). We performed blood leukocyte counts and in vitro culture. Cytokine levels in the supernatants (CBA), serum total IgE and anti-Asc IgE (ImmunoCAP), IgG1, IgG4, and total IgA (ELISA) were measured. Infection was not associated with allergy. Infected children showed increased levels of anti-Asc IgG1, IL-2, IFN-γ, IL-4, and IL-10. There was a lower frequency of allergy-related symptoms in anti-Asc IgG1-positive children than IgG1-negative (OR = 0.38; CI = 0.17-0.90, p = 0.027) and few eosinophils in G-RA than in G-nRA and more in G-nRA than in nG-nRA, whereas TNF-α levels were higher in the G-RA than in the nG-nRA group. For infected and positive anti-Asc IgG1, there was higher TNF-α and IL-10 production than G/-IgG1. IL-10 levels were lower in nG/ + IgG1 than in infected or non-infected, and both were negative for anti-Asc IgG1. Th1/Th2/IL-10 profiles were stimulated in the infected patients, and in those with circulating anti-Asc IgG1, the TNF-α production was strengthened with a lower risk for respiratory allergy symptoms.

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Giardia lamblia is a highly infectious protozoan that causes giardiasis, a gastrointestinal disease with short-term and long-lasting symptoms. The currently available drugs for giardiasis treatment have limitations such as side effects and drug resistance, requiring the search for new antigiardial compounds. Drug repurposing has emerged as a promising strategy to expedite the drug development process. In this study, we evaluated the cytotoxic effect of terfenadine on Giardia lamblia trophozoites. Our results showed that terfenadine inhibited the growth and cell viability of Giardia trophozoites in a time-dose-dependent manner. In addition, using scanning electron microscopy, we identified morphological damage; interestingly, an increased number of protrusions on membranes and tubulin dysregulation with concomitant dysregulation of Giardia GiK were observed. Importantly, terfenadine showed low toxicity for Caco-2 cells, a human intestinal cell line. These findings highlight the potential of terfenadine as a repurposed drug for the treatment of giardiasis and warrant further investigation to elucidate its precise mechanism of action and evaluate its efficacy in future research.

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Giardia lamblia (G. lamblia) is the main causative agent of diarrhea worldwide, affecting children and adults alike; in the former, it can be lethal, and in the latter a strong cause of morbidity. Despite being considered a predominant disease in low-income and developing countries, current migratory flows have caused an increase in giardiasis cases in high-income countries. Currently, there is a wide variety of chemotherapeutic treatments to combat this parasitosis, most of which have potentially serious side effects, such as genotoxic, carcinogenic, and teratogenic. The necessity to create novel treatments and discover new therapeutic targets to fight against this illness is evident. The current review centers around the controversial nucleolus of G. lamblia, providing a historical perspective that traces its apparent absence to the present evidence supporting its existence as a subnuclear compartment in this organism. Additionally, possible examples of ncRNAs and proteins ubiquitous to the nucleolus that can be used as targets of different therapeutic strategies are discussed. Finally, some examples of drugs under research that could be effective against G. lamblia are described.