Search Results (748)

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation. Full article

Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

In this study, an in vitro co-culture system of Castilleja tenuiflora and its host, Baccharis conferta, was used, and the impact of their interaction on specialized metabolite content was analyzed. After 4 weeks of co-culture, haustoria formation was verified through environmental scanning electron and confocal microscopy, confirming the successful establishment of the plant–plant interaction. Shoot height and biomass of the aerial part of the hemiparasite were not affected significantly by co-culture. However, root biomass increased by 53% compared to individually grown plants. Co-culture significantly reduced the host’s root length without negatively affecting its overall growth or survival. Phytochemical profile alterations were observed in both species. For C. tenuiflora, the lignans sesamin and eudesmin are proposed as differentially accumulated metabolites, while in B. conferta, the caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, and the flavonoid acacetin were expressed differently. The development and chemical profiles of B. conferta and C. tenuiflora change when they grow in a co-culture because of the host–parasite interaction. Here, we report the feasibility of using a hemiparasite–host system to investigate more profound research questions. Future biotechnological applications of this system include elucidating the genetic regulators involved in haustorium formation, as well as optimizing environmental and physiological conditions to enhance its biosynthetic capacity for the production of specialized metabolites with therapeutic value. Full article

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

Host selectivity or preference plays a critical role in enabling parasitic plants to identify suitable hosts and influence plant community dynamics. Phosphorus (P) is known to affect the growth of root hemiparasitic plants and their interaction with single host species, but its role in shaping host selectivity across multiple hosts is unclear. In a pot experiment, we used a grass–legume co-culture design and evaluated whether the root hemiparasitic plant Pedicularis kansuensis exhibits selective parasitism on legumes (Medicago sativa) versus grasses (Elymus nutans) and assessed the impact of soil P availability on this preference. The results showed that P. kansuensis inhibited the growth of both host species, but the magnitude of suppression varied with P availability. Under low P conditions, P. kansuensis preferentially parasitized the tender M. sativa, causing a greater biomass reduction in the legume. In contrast, at high P levels, P. kansuensis decreased its foraging on legumes, shifting its parasitism towards the dominant E. nutans, which potentially led to stronger suppression of grass growth. Our findings demonstrate that soil P availability modulates host selectivity in P. kansuensis, emphasizing the influence of soil nutrient conditions on parasite–host dynamics. This research provides insights into managing the impacts of parasitic plants on plant community structure through nutrient interventions. Full article

Background: Bovine babesiosis, caused by the tick-borne apicomplexan parasite Babesia spp., is an economically significant disease that threatens the cattle industry worldwide. Babesia bovis is the most pathogenic species, leading to high morbidity and mortality in infected animals. One promising approach to vaccination against bovine babesiosis involves the use of multiple protective antigens, offering advantages over traditional live-attenuated vaccines. Tools such as immunobioinformatics and reverse vaccinology have facilitated the identification of novel antigens. Enolase, a “moonlighting” enzyme of the glycolytic pathway with demonstrated vaccine potential in other pathogens, has not yet been studied in B. bovis. Methods: In this study, the enolase gene from two B. bovis isolates was successfully identified and sequenced. The gene, consisting of 1366 base pairs, encodes a predicted protein of 438 amino acids. Its expression in intraerythrocytic parasites was confirmed by RT-PCR. Two peptides containing predicted B-cell epitopes were synthesized and used to immunize rabbits. Hyperimmune sera were then analyzed by ELISA, confocal microscopy, Western blot, and an in vitro neutralization assay. Results: The hyperimmune sera showed high antibody titers, reaching up to 1:256,000. Specific antibodies recognized intraerythrocytic merozoites by confocal microscopy and bound to a ~47 kDa protein in erythrocytic cultures of B. bovis as detected by Western blot. In the neutralization assay, antibodies raised against peptide 1 had no observable effect, whereas those targeting peptide 2 significantly reduced parasitemia by 71.99%. Conclusions: These results suggest that B. bovis enolase contains B-cell epitopes capable of inducing neutralizing antibodies and may play a role in parasite–host interactions. Enolase is therefore a promising candidate for further exploration as a vaccine antigen. Nonetheless, additional experimental studies are needed to fully elucidate its biological function and validate its vaccine potential. 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

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti-Naegleria activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the N. fowleri trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against N. fowleri infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host–pathogen interactions critical to PAM pathogenesis. Full article

Leishmaniasis, caused by protozoan parasites of the genus Leishmania, is one of the most neglected human diseases, affecting millions worldwide. A detailed understanding of the molecular mechanisms that govern the outcome of macrophage–Leishmania interactions is crucial for a comprehensive understanding of leishmaniasis; however, our current knowledge of these mechanisms remains limited. It is clear that Leishmania has co-evolved to engage several clever strategies to regulate the cell biology of host macrophages to survive and multiply in phagolysosomes of these cells. In this review, we discuss how Leishmania exploits the macrophage Yin-Yang 1 protein as a critical proxy virulence factor to promote its survival. Additionally, we discuss an atlas of YY1-dependent proteins in human macrophages, which could serve as a valuable resource for researchers studying the role of YY1 in macrophage cell biology. Full article

The honey bee is a crucial pollinator in urban ecosystems but faces multiple challenges, including habitat degradation, pollution, and parasitism by species such as the phorid fly, Apocephalus borealis Brues (Diptera: Phoridae). This study investigated honey bee abundance and the percentage of A. borealis parasitism in an urban environment in San Francisco, California. We monitored six sites weekly for six months using two sampling methods. Individual bees were weighed and observed for parasitoid emergence under controlled laboratory conditions. Our results indicate fluctuations in honey bee parasitism by A. borealis from September 2024 to May 2025, with four distinct peaks occurring in mid-September, February, late March, and early May. The highest parasitism rates exceeded 50% in early May, coinciding with increased temperatures and drops in relative humidity. These results suggest a potential link between abiotic conditions and parasitoid activity, highlighting the importance of long-term monitoring to understand the seasonal dynamics of host–parasite interactions in urban environments. Full article

Plant microbiomes are vital for the growth and health of their host. Tree-associated microbiomes are shaped by multiple factors, of which the host is one of the key determinants. Whether different host genotypes affect the structure and diversity of the tissue-associated microbiome and how specific taxa enriched in different tree tissues are not yet well illustrated. Chinese fir (Cunninghamia lanceolata) is an important tree species for both economy and ecosystem in the subtropical regions of Asia. In this study, we investigated the tissue-specific fungal community structure and diversity of nine different Chinese fir genotypes (39 years) grown in the same field. With non-metric multidimensional scaling (NMDS) analysis, we revealed the divergence of the fungal community from rhizosphere soil (RS), fine roots (FRs), and thick roots (TRs). Through analysis with α-diversity metrics (Chao1, Shannon, Pielou, ACE, Good‘s coverage, PD-tree, Simpson, Sob), we confirmed the significant difference of the fungal community in RS, FR, and TR samples. Yet, the overall fungal community difference was not observed among nine genotypes for the same tissues (RS, FR, TR). The most abundant fungal genera were Russula in RS, Scytinostroma in FR, and Subulicystidium in TR. Functional prediction with FUNGuild analysis suggested that ectomycorrhizal fungi were commonly enriched in rhizosphere soil, while saprotroph–parasite and potentially pathogenic fungi were more abundant in root samples. Specifically, genotype N104 holds less ectomycorrhizal and pathogenic fungi in all tissues (RS, FR, TR) compared to other genotypes. Additionally, significant correlations of several endophytic fungal taxa (Scytinostroma, Neonothopanus, Lachnum) with the growth traits (tree height, diameter, stand volume) were observed. This addresses that the interaction between tree roots and the fungal community is a reflection of tree growth, supporting the “trade-off” hypothesis between growth and defense in forest trees. In summary, we revealed tissue-specific, as well as host genotype-specific and genotype-common characters of the structure and functions of their fungal communities. Full article

The largest Eurasian rodent, the Eurasian beaver Castor fiber, is known for its amphibious lifestyle that allows it to adapt its environment to its needs. Due to its lifestyle and evolutionary history, the beaver is characterized by a distinct, unique parasitofauna. In this context, the occurrence of mites from the Demodecidae family in the Eurasian beaver was investigated. The topography of the Demodex castoris was analyzed: it was previously known from a single record from a single skin location of this host. The mite was found in large numbers in various locations in the hairy skin, including the head, trunk, and limbs. In addition, a new species associated with hairless skin, mainly around the mouth, was discovered and described: Demodex ovaportans sp. nov. The females of this species carry the egg on the dorsal side of the podosoma, which may be a form of care and a previously unknown reproductive strategy in Demodecidae. Our findings confirm that a host-specific demodecid mite species associated with the hairy skin of the entire body is a universal model in mammals. They also emphasize the uniqueness of the beaver parasitofauna, as evidenced by the host specificity and the different biology of the demodecids described in it. Full article

Stink bugs are widespread agricultural pests that damage crops and reduce yield. Their impact is influenced by host plant selection and interactions with natural enemies, particularly egg parasitoids. Understanding these relationships is crucial for improving biological control strategies. This paper investigates the seasonal host plant use and parasitism of Halyomorpha halys, Palomena prasina, and Pentatoma rufipes in South Tyrol, Italy. Over two years, we conducted field surveys at 27 sites, recording stink bug presence across 85 plant species and analyzing egg parasitism rates. Results show that stink bugs exhibit distinct host plant preferences, with H. halys utilizing the broadest range of host plants while P. prasina and P. rufipes showed stronger affinities for specific families such as Sapindaceae and Rosaceae. Parasitism rates varied across species and plant families: Trissolcus japonicus predominantly parasitized H. halys while T. cultratus and two Telenomus species targeted P. rufipes and P. prasina, respectively. Spatial–temporal features and host plant associations significantly influenced species distributions and parasitoid occurrence. These findings emphasize the role of plant–insect interactions in shaping pest and parasitoid dynamics. Integrating plant diversity into pest management strategies could enhance parasitoid effectiveness and reduce stink bug populations, contributing to more sustainable agricultural practices. Full article