Search Results (524)

Schistosoma mansoni infection is associated with hepatic inflammation and fibrosis, but its systemic metabolic effects remain poorly understood. This study aimed to investigate changes in the serum lipidomic profile associated with S. mansoni infection and parasite load in individuals from an endemic area. This cross-sectional analysis was nested within a longitudinal cohort study conducted in northeastern Brazil. Parasitological diagnosis and quantification were performed using the Kato–Katz technique. A total of 45 individuals were selected and divided into three groups: high parasite load (HL), low parasite load (LL), and uninfected controls (NegE). Serum samples were analyzed using mass-spectrometry-based lipidomics. The most abundant lipid subclasses across all groups were phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines (PE). However, individuals in the HL group exhibited distinct lipidomic profiles, with increased levels of specific phosphatidylinositols (PI) and reduced levels of certain TAG species compared to the NegE group. These changes may reflect host–parasite interactions and immune–metabolic alterations driven by intense infection. Our findings suggest that S. mansoni infection, particularly at higher parasite burdens, can influence the host’s serum lipid profile and may contribute to metabolic disturbances in endemic populations. Full article

Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to facilitate its parasitism. In this study, untargeted metabolomics was employed to analyze metabolic changes in cucumber roots following nematode inoculation, with the goal of identifying differentially accumulated metabolites that may influence M. incognita behavior. Metabolomic analysis revealed that M. incognita significantly altered the cucumber root metabolome, triggering an accumulation of lipids and organic acids and enriching biotic stress-related pathways such as alkaloid biosynthesis and linoleic acid metabolism. Among differentially accumulated metabolites, myristic acid and hexadecanal were selected for further study due to their potential roles in nematode inhibition. In vitro assays demonstrated that both metabolites suppressed egg hatching and reduced infectivity of M. incognita, while pot experiments indicated a correlation between their application and reduced root gall formation. Chemotaxis assays further revealed that both metabolites exerted repellent effects on the chemotactic migration of M. incognita J2 and suppressed the transcriptional expression of two motility-and feeding-related neuropeptides, Mi-flp-1 and Mi-flp-18. In conclusion, this study demonstrates the significant potential of differentially accumulated metabolites induced by M. incognita infection for nematode disease control, achieved by interfering with nematode chemotaxis and subsequent infection. This work also provides deeper insights into the metabolomic mechanisms underlying the cucumber-M. incognita interaction. Full article

The apicoplast is a highly specialized organelle in the biosynthesis of essential metabolites in most of the apicomplexan protozoa. This organelle is surrounded by four layers of membranes. However, the molecular mechanisms mediating transmembrane transport are not yet fully understood. In this study, we conducted a phenotypic analysis to investigate the role of a major facilitator superfamily transporter (TgApMFS1) in the survival of the parasite. The results indicated that TgApMFS1 is critical for the survival of Toxoplasma gondii in cell culture conditions. Further analysis indicated that these transporters are crucial for the biogenesis of organelles and the metabolic processes of parasite. Full article

Background: Dyslipidemia and schistosomiasis are major public health challenges, particularly in endemic regions where their coexistence may influence host metabolism and immune responses. This study aimed to evaluate visceral adipose tissue (AT) remodeling in a murine model of acute Schistosoma mansoni infection combined with diet-induced dyslipidemia. Methodology: Female Swiss Webster mice were fed either a standard or high-fat diet (HFD) for 29 weeks and infected with S. mansoni at week 20. Nine weeks after infection, biochemical, morphometric, histopathological, and immunological analyses were performed. Results: The HFD promoted weight gain and dyslipidemia, while S. mansoni infection alone did not alter lipid profiles but partially mitigated the metabolic effects of the HFD. Morphometric analysis revealed adipocyte hypertrophy and reduced cell number in HFD-fed animals. In HFD-fed infected mice, infection partially reversed hypertrophy, suggesting a modulatory effect on AT remodeling. Histopathological examinations showed that while a HFD induced mild inflammation, infection led to intense leukocyte infiltration, hyperemia, and plasma cell degeneration. Peritoneal lavage confirmed a proinflammatory immune profile. Conclusions: These findings indicate that the interaction between a HFD and S. mansoni infection exacerbates adipose tissue inflammation and metabolic alterations, highlighting the complex interplay between parasitic infection, diet, and immune-metabolic regulation. Full article

Global interest in nematode communities and their ecological relationships as unique and complex soil ecosystems has remarkably increased in recent years. As they have a representative role in the soil biota, nematodes present great potential to help understand soil health through analyzing their food chains in different environments. The objective of this study was to analyze the spatial and dynamic distributions of nematode communities and soil properties in two riparian areas of the Caatinga biome: one with native vegetation and the other with a history of agricultural use (modified). The study was carried out in a semi-arid region of Brazil in Parnamirim, PE. In both areas, sampling grids of 60 m × 40 m were established to obtain data on soil moisture, organic matter, particle size, electrical conductivity, and pH, as well as metabolic activity and ecological indices of nematode communities. There was a greater abundance and diversity of nematodes in riparian soils with native vegetation compared to in the modified area due to agricultural use and the dominance of exotic and invasive species. In both areas, bacterivores and plant-parasitic nematodes were dominant, with the genus Acrobeles and Tylenchorhynchus as the main contributors to the community. In the modified area, soil variables (fine sand, clay, and pH) positively influenced Fu4 and PP4 guilds, while in the area with native vegetation, moisture and organic matter exerted a greater influence on Om4, PP5, and Ba3 guilds. Kriging maps showed the soil variables were more concentrated in the center in the areas with native vegetation, in contrast to the area with modified vegetation, where they concentrated more on the margins. The functional guilds in the native vegetation did not exhibit a gradual increase towards the regions close to the riverbank, unlike in the modified area. The presence of plant-parasitic nematodes, especially of the genus Tylenchorhynchus, indicates the need for greater attention in the management of these ecosystems. The study contributes to understanding the interactions between nematode communities and soil in riparian areas of the Caatinga biome, emphasizing the importance of preserving native vegetation to maintain the diversity and balance of this ecosystem, in addition to highlighting the need for appropriate management practices in areas with a history of agricultural use, aiming to conserve soil biodiversity. Full article

Background/Objectives: Leishmaniasis is a zoonotic and anthropozoonotic disease with significant public health impact worldwide and is classified as a neglected tropical disease. The search for new affordable treatments, particularly oral and/or topical ones that are easy to administer and have fewer side effects, remains a priority for the scientific community in this field of research. In previous investigations, 3-alkoxy-1-benzyl-5-nitroindazole derivatives showed remarkable in vitro results against Leishmania species, and predictions of absorption, distribution, metabolism, excretion, and toxicity properties, as well as pharmacological scores, of the compounds classified as active were superior to those of amphotericin B, indicating their potential as candidates for in vivo studies. Therefore, the aim of the present study was to evaluate the in vivo antileishmanial activity of the indazole derivatives NV6 and NV16. Methods: The compounds were administered intralesionally at concentrations of 10 and 5 mg/kg in a BALB/c mouse model of cutaneous leishmaniasis caused by Leishmania amazonensis. To evaluate the efficacy of the compounds, indicators such as lesion size, ulcer area, lesion weight, and parasitic load were determined. Amphotericin B was used as a positive control. Results: The compound NV6 showed leishmanicidal activity comparable to that observed with amphotericin B, with a significant reduction in lesion development and parasite load, while NV16 caused a reduction in ulcer area. Conclusions: These results provide strong evidence for the antileishmanial activity of NV6 and support future studies to improve its pharmacokinetic profile, as well as the investigation of combination therapies with other chemotherapeutic agents currently in use. Full article

Hair, as a non-invasive biospecimen, retains metabolic deposits from sebaceous glands and capillaries, reflecting substances from the peripheral circulation, and provides valuable biochemical information linked to phenotypes, yet its application in animal disease research remains limited. This work applied ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) to compare the hair metabolomic characteristics of healthy forest musk deer (FMD, Moschus berezovskii) and those diagnosed with hemorrhagic pneumonia (HP), phytobezoar disease (PD), and abscess disease (AD). A total of 2119 metabolites were identified in the FMD hair samples, comprising 1084 metabolites in positive ion mode and 1035 metabolites in negative ion mode. Differential compounds analysis was conducted utilizing the orthogonal partial least squares–discriminant analysis (OPLS-DA) model. In comparison to the healthy control group, the HP group displayed 85 upregulated and 92 downregulated metabolites, the PD group presented 124 upregulated and 106 downregulated metabolites, and the AD group exhibited 63 upregulated and 62 downregulated metabolites. Functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the differential metabolites exhibited significant enrichment in pathways associated with cancer, parasitism, energy metabolism, and stress. Receiver operating characteristic (ROC) analysis revealed that both the individual and combined panels of differential metabolites exhibited area under the curve (AUC) values exceeding 0.7, demonstrating good sample discrimination capability. This research indicates that hair metabolomics can yield diverse biochemical insights and facilitate the development of non-invasive early diagnostic techniques for diseases in captive FMD. Full article

Meloidogyne incognita (M. incognita) is a devastating root-knot nematode that parasitizes a broad range of crop species by inducing the formation of giant cells (GCs) in host roots, thereby facilitating nutrient acquisition. This process profoundly alters host sugar metabolism, yet the molecular regulators underlying sugar dynamics during infection remain poorly understood in cucumber. In this study, we investigated the role of the cucumber alkaline α-galactosidase gene (CsAGA1) in M. incognita-infected roots. Histochemical analysis of proCsAGA1::GUS transgenic lines demonstrated that CsAGA1 is spatially localized to nematode-induced feeding sites, with its expression markedly induced in GCs and phloem-adjacent tissues during infection. Functional analyses revealed that silencing CsAGA1 impaired root and gall development. CsAGA1-silenced plants exhibited increased gall numbers (per gram root) but significantly reduced root growth and smaller galls compared to controls. These results indicate that CsAGA1 is required for proper gall expansion and root growth during M. incognita infection. This study provides novel insight into the sugar-mediated regulation of host–nematode interactions, and CsAGA1 emerges as a potential target for the biological control of M. incognita. Full article

Serious enteric disease caused by seven species of Eimeira continues to cause significant economic damage to the poultry industry. E. acervulina is one of the most widespread strains in farms and has a significant impact on chicken weight loss. Currently, the use of anticoccidial agents to suppress the occurrence of coccidiosis in farms is considerably restricted due to public health and environmental pollution issues. It is important to understand the protective immunity of the host against Eimeria infections with regard to natural products that could be used as alternatives to anticoccidial agents. Berberine chloride is known for its various biological functions, including its anti-parasite activity. However, its impact on intestinal morphology and immune-related activity in broilers infected with Eimeria still remains unclear. The aim of this study is to evaluate the anticoccidial effects of a berberine-based diet in broilers infected with E. acervulina and to monitor the host immune phenomenon using transcriptomic analysis. Administration of berberine to chickens infected with E. acervulina significantly reduced fecal oocyst production and intestinal lesion scores, and increased duodenal villus height, indicating anticoccidial activity and positive effects on intestinal morphology. Transcriptomic analysis of chickens infected with E. acervulina generally observed the down-regulation of metabolism-related genes and the up-regulation of cell integrity-related genes at day 4 post-infection. At day 6 post-infection, an increase in immune-related genes and cellular-homeostasis-related genes was generally observed. Berberine-treated and E. acervulina-infected chickens showed cytokine-cytokine receptor interaction in the second term in a Kyoto Encyclopedia of Genes and Genomes pathway analysis at day 4 post-infection, but not in chickens infected with E. acervulina alone, suggesting host immune changes induced by berberine. These results suggest that berberine, which exhibits anticoccidial effects, may have therapeutic and/or prophylactic potential in protecting the host from infectious and economic-loss-causing diseases, such as Eimeria infection. Full article

Trypanosoma cruzi is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of T. cruzi, with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5′-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in T. cruzi may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease. Full article

Disease-suppressive soils confer fitness advantages to plants after a disease outbreak due to the subsequent assembly of protective microbiota in natural environments. However, the role of ecological effects on the assemblage of a protective soil microbiome is largely elusive. In this study, we investigated the composition of parasitic microbes and their relationships with soybean cyst nematodes in suppressive soil. The results showed that parasitic microbial assembly along soybean cyst nematodes was shaped predominantly by the density of soybean cyst nematodes. We also found soybean continuous cropping increased the number of parasitic microbes of soybean cyst nematodes with the order of Ss > Sr > Sc, while it decreased the population of soybean cyst nematodes, resulting in a natural decline in the number of soybean cyst nematodes. These findings indicate that the population of soybean cyst nematodes accumulated parasitic microorganisms against this soil-borne disease under soybean long-term continuous cropping. Moreover, the metabolic activity of cyst parasitic microbes was increased by two years of continuous cropping (Sc) of soybean, and total carbon and total nitrogen of soil were the main impact factors in this short-term continuous cropping for metabolic patterns of the cyst parasitic microbes. In summary, the results highlight that the interaction of plants and disease shape the soil microbiome, recruit a group of disease resistance-inducing microbes, and modulate their beneficial traits to protect the plant. Full article

Trichlorfon is an antiparasitic agent widely used to control pests and parasites in farmed fish. Tambaqui (C. macropomum) is the most commercially important characid species farmed in the Amazon region. Trichlorfon exposure is known to cause physiological damage in fish due to its organophosphate nature. In this study, we used RNA-Seq to investigate the hepatic response of tambaqui following exposure to 0.435 mg/L of trichlorfon. The analysis revealed activation of several metabolic pathways, particularly those related to tumor processes, immune responses, and apoptosis. Additionally, we identified upregulation of solute carrier (SLC) genes, which may facilitate trichlorfon entry into hepatocytes. These findings enhance our understanding of fish responses to antiparasitic agents and support further research into the molecular impacts of organophosphate compounds in aquaculture species. Full article

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), continues to pose significant public health challenges due to the toxicity, poor tolerability, and limited efficacy of current treatments. Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) represents a novel therapeutic avenue by leveraging the ubiquitin–proteasome system to selectively degrade essential parasite proteins. This review introduces the conceptual framework of “TrypPROTACs” as a prospective strategy for T. cruzi, integrating a comprehensive analysis of druggable targets across critical biological pathways, including ergosterol biosynthesis, redox metabolism, glycolysis, nucleotide synthesis, protein kinases, molecular chaperones such as heat shock protein 90 (Hsp90), and epigenetic regulators such as T. cruzi bromodomain factor 3 (TcBDF3). It is important to note that no TrypPROTAC compound has yet been synthesized or experimentally validated in T. cruzi; the approach discussed herein remains theoretical and forward-looking. Representative inhibitors for each target class are compiled, highlighting potency, selectivity, and structural features relevant to ligand design. We also examine the parasite’s ubiquitination machinery and compare it to the human system to identify putative E3 ubiquitin ligases. Key aspects of linker engineering and ternary complex stabilization are discussed, alongside potential validation techniques such as the cellular thermal shift assay (CETSA) and bioluminescence resonance energy transfer (NanoBRET). Collectively, these insights outline a roadmap for the rational design of TrypPROTACs and support the feasibility of expanding targeted protein degradation strategies to neglected tropical diseases. Full article

Dermatophytosis is a fungal infection that affects the skin, hair, and nails, impacting approximately 25% of the global population. Nannizzia gypsea is a geophilic fungus that can cause infections in humans and animals. Several studies have been conducted regarding its virulence, or ability to cause disease. This species may produce keratinolytic enzymes and form biofilms, which can increase resistance to treatment. Thus, this study focuses on investigating the biofilm formation of N. gypsea isolated from canine dermatophytosis using an ex vivo hair model, its biofilm extracellular matrix macromolecular contents, and the expression of genes involved in the colonization of keratinized surfaces. The biofilm was analyzed for metabolic activity using the XTT reduction assay, crystal violet staining to measure biofilm biomass, scanning electron microscopy (SEM), and the presence of polysaccharides, proteins, and extracellular DNA in the biofilm extracellular matrix. The virulence genes subtilisin 7, fungalysin (extracellular metalloproteinase), and efflux pump (Multidrug and Toxin Extrusion Protein 2) were evaluated by qPCR, comparing the planktonic and biofilm phenotypes. N. gypsea formed a robust biofilm, which matured after 5 days. Scanning electron microscopy (SEM) revealed the presence of an extensive extracellular matrix. In the hair model, the characteristic ectothrix parasitism of the species is observable. The gene expression analysis revealed a higher expression of all evaluated genes in the biofilm form compared to the planktonic form. Thus, N. gypsea exhibits a biofilm characterized by a robust extracellular matrix and high gene expression of factors related to pathogenesis and resistance. Full article

Alveolar echinococcosis (AE) is a chronic and potentially fatal zoonotic parasitic disease that seriously affects the host’s health. It is caused by the proliferation of Echinococcus multilocularis larvae within the liver. Due to its long incubation period following host infection, early diagnosis of the disease is currently not feasible. Treatment options are extremely limited, with the only choice being curative surgical resection combined with benzimidazole medication. Thus, the development of early, rapid, and minimally invasive diagnostic methods is crucial for enhancing patient prognosis. This study conducted proteomic and metabolomic analyses of protein and metabolite changes in the serum of a treatment group and control group, aiming to compare the differences between them. Overall, 22 proteins showed significant differences between the treatment and control groups, primarily involved in carbohydrate metabolism, lipid metabolism, and amino acid metabolism. The upregulation of genes related to immune response and enhanced glycolysis were observed, possibly associated with the reproduction of E. multilocularis in the liver. A total of 182 metabolites were screened to distinguish between the treatment group and control group. A significant increase in the cytochrome P450 (cP450) metabolite of arachidonic acid indicated signs of renal and splenic involvement in the treatment group. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted a strong association between amino acid metabolism and the development of AE. The observed changes in amino acid levels may provide nutrients that facilitate E. multilocularis colonization and contribute to the pathogenesis of AE. In summary, by investigating the different characteristics of the AE and control group through proteomic (n = 4/group/time point) and metabolomic (n = 8/group/time point) analyses, potential serum biomarkers for diagnosing mice with AE were identified. Full article