Complete genomes of the eukaryotic poultry parasite Histomonas meleagridis: linking sequence analysis with virulence / attenuation

Abstract Background Histomonas meleagridis is a protozoan parasite and the causative agent of histomonosis, an important poultry disease whose significance is underlined by the absence of any treatment and prophylaxis. The recent successful in vitro attenuation of the parasite urges questions about the underlying mechanisms. Results Whole genome sequence data from a virulent and an attenuated strain originating from the same parental lineage of H. meleagridis were recruited using Oxford Nanopore Technology (ONT) and Illumina platforms, which were combined to generate megabase-sized contigs with high base-level accuracy. Inspecting the genomes for differences identified two substantial deletions within a coding sequence of the attenuated strain. Additionally, one single nucleotide polymorphism (SNP) and indel targeting coding sequences caused the formation of premature stop codons, which resulted in the truncation of two genes in the attenuated strain. Furthermore, the genome of H. meleagridis was used for characterizing protein classes of clinical relevance for parasitic protists. The comparative analysis with the genomes of Trichomonas vaginalis, Tritrichomonas foetus and Entamoeba histolytica identified ~ 2700 lineage-specific gene losses and 9 gene family expansions in the H. meleagridis lineage. Conclusions Taken as a whole, the obtained data provide the first hints to understand the molecular basis of attenuation in H. meleagridis and constitute a genomics platform for future research on this important poultry pathogen.

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Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1379531 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

YinYing Ba ◽

MengLin Wang ◽

KunFeng Zhang ◽

QiJun Chen ◽

JiaJia Wang ◽

...

Keyword(s):

Future Research ◽

Active Components ◽

Sodium Caprate ◽

P Glycoprotein ◽

Paracellular Absorption ◽

Underlying Mechanisms ◽

The Relationship ◽

Rat Gut ◽

Human Nervous System

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6′-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS’s absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

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CSF1R-related leukoencephalopathy

Neurology ◽

10.1212/wnl.0000000000006642 ◽

2018 ◽

Vol 91 (24) ◽

pp. 1092-1104 ◽

Cited By ~ 23

Author(s):

Takuya Konno ◽

Koji Kasanuki ◽

Takeshi Ikeuchi ◽

Dennis W. Dickson ◽

Zbigniew K. Wszolek

Keyword(s):

White Matter ◽

Cultured Cells ◽

Clinical Symptoms ◽

Current Knowledge ◽

Gene Mutations ◽

Future Research ◽

Primary Role ◽

Extrapyramidal Signs ◽

Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

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Infection with the intracellular protozoan parasite Theileria parva induces constitutively high levels of NF-kappa B in bovine T lymphocytes

Molecular and Cellular Biology ◽

10.1128/mcb.9.11.4677-4686.1989 ◽

1989 ◽

Vol 9 (11) ◽

pp. 4677-4686

Author(s):

V Ivanov ◽

B Stein ◽

I Baumann ◽

D A Dobbelaere ◽

P Herrlich ◽

...

Keyword(s):

T Cells ◽

Phorbol Esters ◽

Protozoan Parasite ◽

Lymphoproliferative Disease ◽

Host Cells ◽

Specific Gene ◽

Theileria Parva ◽

Nf Kappa B ◽

Intracellular Protozoan Parasite

The intracellular protozoan parasite Theileria parva causes a lymphoproliferative disease of T cells in cattle and uncontrolled lymphocyte proliferation in culture. We have identified and characterized in infected cells the transcriptional activator, NF-kappa B, whose recognition motifs have been identified in several gene enhancers important for lymphocyte-specific gene expression. NF-kappa B is normally constitutively activated in nuclear extracts derived from B cells and can be induced in T cells and nonlymphoid cells by phorbol esters. Theileria-infected lymphocytes contained constitutively high levels of activated NF-kappa B in nuclear fractions and inactive NF-kappa B in cytoplasmic fractions. The inactive cytoplasmic precursor could be activated by treatment of extracts with deoxycholate, which was shown previously to dissociate NF-kappa B from an inhibitor, I kappa B. Treatment of lymphocyte extracts with 3 mM GTP stimulated NF-kappa B binding to its recognition motif in vitro, thereby distinguishing it from a related nuclear factor, H2-TF1. Selective killing of the parasite, which left the host cells intact, resulted in a rapid loss of NF-kappa B from the nuclear fractions and a slower loss from the cytoplasmic fractions. In parasitized cells, NF-kappa B could not be further stimulated by treatment with 12-O-tetradecanoylphorbol-13-acetate whereas in cells treated to remove the parasite, this compound stimulated elevated levels of NF-kappa B. We propose that high levels of activated NF-kappa B are maintained by the presence of the parasite in infected T cells. Similarly, we propose that the high levels of inactive cytoplasmic precursor are a result of increased synthesis due to the presence of the parasite.

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A Review on Herbal Treatments for Trichomonas Vaginalis

Tabari Biomedical Student Research Journal ◽

10.18502/tbsrj.v3i2.6673 ◽

2021 ◽

Author(s):

Fatemeh Rahmani ◽

Yahya Ehteshaminia ◽

Hamid Mohammadi ◽

Seif Ali Mahdavi

Keyword(s):

Side Effects ◽

Trichomonas Vaginalis ◽

Transmitted Disease ◽

Protozoan Parasite ◽

Patient Acceptance ◽

Therapeutic Effects ◽

Men And Women ◽

Sexually Transmitted ◽

Advantages And Disadvantages

Introduction: Trichomonas vaginalis is a protozoan parasite that infects the urogenital tract of men and women and causes trichomoniasis, a common sexually transmitted disease in both men and women. The infection is often asymptomatic, but it can be accompanied by symptoms such as severe inflammation, itching and burning, foamy discharge and foul-smelling mucus. In one year, 250 million cases of Trichomonas vaginalis were reported worldwide. Material and Methods: In this study, the websites of PubMed, Google Scholar, SID, and Margiran were searched and related articles were reviewed. Results: Today, the most common treatment for this disease is the use of metronidazole. However, its side effects, which include hematological and neurotoxic effects, cannot be ignored. Because of these side effects, researchers are looking for a suitable replacement for metronidazole in the treatment of trichomoniasis. Researchers' desire to use herbs can be due to various reasons such as fewer side effects, better patient acceptance, recommendation of traditional medicine, lower prices of herbs and also compatibility with the normal physiological function of the human body. Conclusion: Considering the inhibitory effects of medicinal plants on the growth and proliferation of Trichomonas vaginalis in vitro, it can be concluded that the use of these plants can have many applications in the treatment of trichomoniasis. As a result, by studying more about their advantages and disadvantages, it is possible to make a drug that has higher therapeutic effects with fewer side effects.

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Zinc-clotrimazole complexes are effective against Trichomonas vaginalis

Parasitology ◽

10.1017/s003118201900043x ◽

2019 ◽

Vol 146 (9) ◽

pp. 1206-1216 ◽

Cited By ~ 1

Author(s):

Victor Midlej ◽

Felipe Rubim ◽

Wilmer Villarreal ◽

Érica S. Martins-Duarte ◽

Maribel Navarro ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Transmitted Disease ◽

Protozoan Parasite ◽

Parasite Resistance ◽

Zinc Compounds ◽

Sexually Transmitted ◽

Transmission Electron ◽

Zinc Salts ◽

Imidazole Compounds

AbstractTrichomonas vaginalis is a protozoan parasite that causes trichomoniasis in humans, the most prevalent non-viral sexually transmitted disease (STD). Imidazole compounds are used for the treatment of trichomoniasis, and metronidazole is the most commonly prescribed. However, these compounds can lead to parasite resistance and unwanted side effects. Therefore, there is a need for an alternative treatment for this disease. Here, we explored the potential of clotrimazole (CTZ) and zinc compounds, as well as CTZ complexed with zinc salts ([1] acetate [Zn(CTZ)2(Ac)2] and [2] a chloride [Zn(CTZ)2Cl2] complexes) against T. vaginalis. We synthesized the zinc complexed CTZ compounds and determined their concentration values that inhibited parasite growth by 50% (IC50). We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by CTZ and their zinc complexes. The incubation of the parasites with [Zn(CTZ)2(Ac)2] complex inhibited their growth, yielding an IC50 of 4.9 µm. Moreover, there were changes in the shape of treated parasites, including the formation of surface projections that subsequently detached from the cell, in addition to changes in the hydrogenosomes, endoplasmic reticulum and Golgi complex. We found [Zn(CTZ)2(Ac)2] to be a highly effective compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.

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Genome Sequence Data of the Soybean Pathogen Stagonosporopsis vannaccii: A Resource for Studies on Didymellaceae Evolution

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-01-20-0016-a ◽

2020 ◽

Vol 33 (8) ◽

pp. 1022-1024

Author(s):

Giovanni Cafà ◽

Thaís Regina Boufleur ◽

Renata Rebellato Linhares de Castro ◽

Nelson Sidnei Massola ◽

Riccardo Baroncelli

Keyword(s):

Comparative Genomics ◽

Genome Sequence ◽

Plant Pathogens ◽

Sequence Data ◽

Gene Prediction ◽

Whole Genome Sequence ◽

Future Research ◽

Whole Genome ◽

Genome Sequence Data ◽

Associated Species

The genus Stagonosporopsis is classified within the Didymellaceae family and has around 40 associated species. Among them, several species are important plant pathogens responsible for significant losses in economically important crops worldwide. Stagonosporopsis vannaccii is a newly described species pathogenic to soybean. Here, we present the draft whole-genome sequence, gene prediction, and annotation of S. vannaccii isolate LFN0148 (also known as IMI 507030). To our knowledge, this is the first genome sequenced of this species and represents a new useful source for future research on fungal comparative genomics studies.

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Trifluoromethionine, a Prodrug Designed against Methionine γ-Lyase-Containing Pathogens, Has Efficacy In Vitro and In Vivo against Trichomonas vaginalis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.6.1743-1745.2001 ◽

2001 ◽

Vol 45 (6) ◽

pp. 1743-1745 ◽

Cited By ~ 49

Author(s):

Graham H. Coombs ◽

Jeremy C. Mottram

Keyword(s):

Drug Target ◽

Trichomonas Vaginalis ◽

Anaerobic Bacteria ◽

Protozoan Parasite ◽

Chemotherapeutic Agents ◽

Single Step ◽

Lesion Formation ◽

Highly Active

ABSTRACT Methionine γ-lyase, the enzyme which catalyzes the single-step conversion of methionine to α-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasiteTrichomonas vaginalis, to anaerobic bacteria containing methionine γ-lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.

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The emerging role of lactate as a mediator of exercise-induced appetite suppression

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00256.2020 ◽

2020 ◽

Vol 319 (4) ◽

pp. E814-E819

Author(s):

Seth F. McCarthy ◽

Hashim Islam ◽

Tom J. Hazell

Keyword(s):

Overweight And Obesity ◽

Future Research ◽

Ghrelin Receptor ◽

Cellular Models ◽

Regulatory Molecule ◽

Blood Lactate Accumulation ◽

Underlying Mechanisms ◽

Exercise Induced

Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significant attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent human studies that have utilized exercise intensity and/or sodium bicarbonate supplementation to modulate endogenous lactate and examine its impact on appetite regulation. These studies consistently demonstrate that greater blood lactate accumulation is associated with greater suppression of the hunger hormone ghrelin and subjective appetite, thereby supporting a role of lactate in the control of EI. To stimulate future research investigating the role of lactate as an appetite-regulatory molecule, we also highlight potential underlying mechanisms explaining the appetite-suppressive effects of lactate using evidence from rodent and in vitro cellular models. Specifically, we discuss the ability of lactate to 1) inhibit the secretory function of ghrelin producing gastric cells, 2) modulate the signaling cascades that control hypothalamic neuropeptide expression/release, and 3) inhibit signaling through the ghrelin receptor in the hypothalamus. Unravelling the role of lactate as an appetite-regulatory molecule can shed important insight into the regulation of EI, thereby contributing to the development of interventions aimed at combatting overweight and obesity.

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In vitro effect of tinidazole and furazolidone on metronidazole-resistant Trichomonas vaginalis.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.5.1121 ◽

1996 ◽

Vol 40 (5) ◽

pp. 1121-1125 ◽

Cited By ~ 68

Author(s):

E M Narcisi ◽

W E Secor

Keyword(s):

Trichomonas Vaginalis ◽

Drug Efficacy ◽

Protozoan Parasite ◽

Enteric Bacteria ◽

Sexually Transmitted ◽

Drug Of Choice ◽

Immunodeficiency Virus ◽

Placental Membranes ◽

Vitro Effect

Trichomonas vaginalis is a common sexually transmitted protozoan parasite. Although often considered simply a nuisance infection, T. vaginalis has been implicated in premature rupture of placental membranes and increases in the risk of acquiring human immunodeficiency virus. Metronidazole, a 5-nitroimidazole, is currently the drug of choice to treat T. vaginalis infection. Because some patients have severe reactions to metronidazole and others are infected with metronidazole-resistant T. vaginalis, we were prompted to investigate alternative therapies. Tinidazole, another 5-nitroimidazole used in other countries to treat T. vaginalis infections, and furazolidone, a nitrofuran presently used to treat giardiasis and infections with some anaerobic enteric bacteria, were investigated for effectiveness against 9 metronidazole-susceptible and 12 metronidazole-resistant T. vaginalis patient isolates. The in vitro aerobic and anaerobic minimum lethal concentrations (MLC) and the time for drug efficacy were determined. Tinidazole killed the metronidazole-susceptible isolates at a low MLC but was effective against only 4 of the 12 metronidazole-resistant isolates. In contrast, furazolidone was effective at a low MLC for all isolates. When tinidazole was effective, it required > 6 h to kill trichomonads. However, furazolidone killed both metronidazole-susceptible and resistant trichomonads within 2 to 3 h of exposure. These data suggest that furazolidone may be a good candidate for treating metronidazole-resistant trichomoniasis and that further investigation of this drug is warranted.

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