Antiproliferative and Morphological Analysis Triggered by Drugs Contained in the Medicines for Malaria Venture COVID-Box Against Tachyzoites.

is a protozoan, and the etiologic agent of toxoplasmosis, a disease that causes high mortality in immunocompromised individuals and newborns. Despite the medical importance of toxoplasmosis, few drugs, which are associated with side effects and parasite resistance, are available for its treatment. Here, we show a screening of molecules present in COVID-Box to discover new hits with anti- activity.

Inflammatory response and parasite regulation in acute toxoplasmosis: the role of P2X7 receptor in controlling virulent atypical genotype strain of .

Toxoplasmosis is a globally significant disease that poses a severe threat to immunocompromised individuals, especially in Brazil, where a high prevalence of virulent and atypical strains of is observed. In 1998, the EGS strain, exhibiting a unique infection phenotype, was isolated in Brazil, adding to the complexity of strain diversity. The P2X7 receptor is critical in inflammation and controlling intracellular microorganisms such as However, its genetic variability can result in receptor dysfunction, potentially worsening susceptibility.

Potent hydroxamate-derived compounds arrest endodyogeny of Toxoplasma gondii tachyzoites.

Toxoplasmosis is a zoonosis that is a worldwide health problem, commonly affecting fetal development and immunodeficient patients. Treatment is carried out with a combination of pyrimethamine and sulfadiazine, which can cause cytopenia and intolerance and does not lead to a parasitological cure of the infection. Lysine deacetylases (KDACs), which remove an acetyl group from lysine residues in histone and non-histone proteins are found in the Toxoplasma gondii genome.

An alternative method to establish an early acute ocular toxoplasmosis model for experimental tests.

Purpose: To provide a simple alternative acute ocular toxoplasmosis model with great reproducibility for experimental tests that demand monitoring of the ocular lesion.

Methods: ME49-wt and ME49-GFP tachyzoites from cell culture were used to infect male C57BL6 mice by intraperitoneal injection. B1 expression by real-time polymerase chain reaction (qPCR) assay was used to detect the presence of T.

P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of -Induced Ileitis.

In mice, oral infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to -induced ileitis. Cysts of the ME49 strain of were used to induce ileitis.

Binding of the extracellular matrix laminin-1 to Clostridioides difficile strains.

Background: Clostridioides difficile is the most common cause of nosocomial diarrhea associated with antibiotic use. The disease's symptoms are caused by enterotoxins, but other surface adhesion factors also play a role in the pathogenesis. These adhesins will bind to components of extracellular matrix.

Characterization of an emergent high-risk KPC-producing Klebsiella pneumoniae lineage causing a fatal wound infection after spine surgery.

Surgical site infections in instrumented posterior lumbar interbody fusion surgery are normally due to gram-positive bacteria, but gram-negative bacteria can cause infections in cases involving lower lumbar interventions as its closer to the perianal area. Here we report an uncommon fatal wound infection caused by a multidrug-resistant Klebsiella pneumoniae after an elective spine surgery. In silico analysis revealed that LWI_ST16 belonged to ST16, an emergent international clone notable for its increased virulence potential.

Dichloroacetate and Pyruvate Metabolism: Pyruvate Dehydrogenase Kinases as Targets Worth Investigating for Effective Therapy of Toxoplasmosis.

Toxoplasmosis, a protozoan infection caused by , is estimated to affect around 2.5 billion people worldwide. Nevertheless, the side effects of drugs combined with the long period of therapy usually result in discontinuation of the treatment.

HDAC inhibitors Tubastatin A and SAHA affect parasite cell division and are potential anti-Toxoplasma gondii chemotherapeutics.

The redirectioning of drugs in the pharmaceutical market is a well-known practice to identify new therapies for parasitic diseases. The histone deacetylase inhibitors Tubastatin A (TST) and Suberoylanilide Hydroxamic Acid (SAHA), firstly developed for cancer treatment, are effective against protozoa parasites. In this work, we aimed to demonstrate the activity of these drugs as potential agents against Toxoplasma gondii, the causative agent of toxoplasmosis.

The life-cycle of Toxoplasma gondii reviewed using animations.

Toxoplasma gondii is a protozoan parasite that is the causative agent of toxoplasmosis, an infection with high prevalence worldwide. Most of the infected individuals are either asymptomatic or have mild symptoms, but T. gondii can cause severe neurologic damage and even death of the fetus when acquired during pregnancy.

Disruption of Purinergic Receptor P2X7 Signaling Increases Susceptibility to Cerebral Toxoplasmosis.

Toxoplasmosis is a neglected disease that affects millions of individuals worldwide. Toxoplasma gondii infection is an asymptomatic disease, with lethal cases occurring mostly in HIV patients and organ transplant recipients. Nevertheless, atypical strains of T.

Identification of the alpha-enolase P46 in the extracellular membrane vesicles of Bacteroides fragilis.

Background: Members of the Bacteroides fragilis group are the most important components of the normal human gut microbiome, but are also major opportunistic pathogens that are responsible for significant mortality, especially in the case of bacteraemia and other severe infections, such as intra-abdominal abscesses. Up to now, several virulence factors have been described that might explain the involvement of B. fragilis in these infections.

The P2X7 Receptor Mediates Control in Macrophages through Canonical NLRP3 Inflammasome Activation and Reactive Oxygen Species Production.

is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world's population. Previously, we showed that purinergic signaling the P2X7 receptor contributes to elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early infection .

A Glycosylphosphatidylinositol-Anchored Carbonic Anhydrase-Related Protein of Is Important for Rhoptry Biogenesis and Virulence.

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism that is related to the recently described η-class CA found in .

Assay to Access Anthelmintic Activity of Small Molecule Drugs Using as a Model.

This protocol proposes to use the nematode as a model to screen and study the anthelmintic activity of natural and synthetic compounds and to observe their effects on the morphology and the ultrastructure of the helminths. Furthermore, can be used to investigate the anthelmintic activity in embryonated eggs, larval stages and in the adults' survival. As most current anthelmintics are not effective against all nematode life stages, this protocol can contribute to the identification of new alternatives to helminthic infections (Sant' Anna , 2016 ).

Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.

Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7 mice are more susceptible than P2X7 mice to acute infection by the RH strain of T.

Anthelmintic effect of herbicidal dinitroanilines on the nematode model Caenorhabditis elegans.

Dinitroanilines are known herbicides that impair the polymerization of microtubules. This study investigated the effects of oryzalin and trifluralin on the viability, morphology, and ultrastructure of different life stages of Caenorhabditis elegans. Both drugs reduced the survival of the adult population in 50% after three days of treatment with concentrations of approximately 30 μM and 57 μM, respectively.

Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages.

Infection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells.

Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound.

Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the treatment of toxoplasmosis.

We propose an innovative product based on the nanoencapsulation of pyrimethamine (PYR), aiming an improvement of drug efficacy for the treatment of toxoplasmosis. The in vitro cytotoxicity effect of encapsulated PYR and PYR-colloidal suspension was concomitantly evaluated against LLC-MK2 lineage and mouse peritoneal macrophage showing that the cells had similar tolerance for both PYR encapsulated or in the aqueous suspension. CF1 mice acutely infected with tachyzoites of Toxoplasma gondii RH strain treated with different doses (5.

Inactivation of a fibronectin-binding TonB-dependent protein increases adhesion properties of Bacteroides fragilis.

Bacteroides fragilis is the Gram-negative strictly anaerobic bacterium most frequently isolated from clinical infections, including intra-abdominal abscess and bacteraemia. A number of factors can contribute to its virulence, including the expression of adhesins. Some of them are already characterized and can recognize and bind to extracellular matrix components, such as fibronectin.

Caenorhabditis elegans as a model for the screening of anthelminthic compounds: ultrastructural study of the effects of albendazole.

This study investigated the effects of albendazole on the viability, morphology and ultrastructure of different life stages of Caenorhabditis elegans. The albendazole EC50 value after seven days of treatment was 18.43 μM.

Toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.

Toxoplasma gondii is an important opportunistic pathogen for immunocompromised patients and responsible for toxoplasmic encephalitis, which is often lethal. Treatment for this infection is limited to a restricted therapeutic arsenal. In this work we tested the combination of fluconazole with the current treatment for acute toxoplasmosis on the murine model in vivo.

The organization of the wall filaments and characterization of the matrix structures of Toxoplasma gondii cyst form.

The encystation process is a key step in Toxoplasma gondii life cycle, allowing the parasite to escape from the host immune system and the transmission among the hosts. A detailed characterization of the formation and structure of the cyst stage is essential for a better knowledge of toxoplasmosis. Here we isolated cysts from mice brains and analysed the cyst wall structure and cyst matrix organization using different electron microscopy techniques.

New details on the fine structure of the rhoptry of Toxoplasma gondii.

Rhoptries are organelles that have important, complex roles in Apicomplexa biology. During Toxoplasma gondii infection, these organelles take part in several essential and complex processes that include host cell entry and parasite development. Using different electron microscopy techniques, we characterized the fine morphology of the rhoptries of two of the most important life stages of T.