Molecular And Biochemical Parasitology[JOURNAL]
Sun
200 papers
Cloning-based analysis of MHC class II DRB variation and Enterocytozoon bieneusi association in the Amur tiger (Panthera tigris altaica).
Liu Y, Xu H, Zhang Y … +10 more , Zhao Y, Lv Z, Liu M, Zhou M, Lu Y, Yu H, Tian H, Zhou S, Tian L, Hou Z
Mol Biochem Parasitol · 2026 Jun · PMID 42336108 · Publisher ↗
The polymorphism of major histocompatibility complex (MHC) class II classical genes is closely related to pathogen resistance, among which the second exon of the DRB gene has the highest variability. In this study, we an...
The polymorphism of major histocompatibility complex (MHC) class II classical genes is closely related to pathogen resistance, among which the second exon of the DRB gene has the highest variability. In this study, we analyzed exon 2 of the MHC class II DRB gene in 32 captive Amur tigers (Panthera tigris altaica) using a cloning-based sequencing approach to assess genetic diversity and its association with infection by Enterocytozoon bieneusi. A total of 16 DRB alleles were identified, including six novel variants. One allele (Pati-DRB*02) showed a significant positive association with infection (P < 0.05), whereas no significant relationship was detected between heterozygosity and infection status. Phylogenetic analysis revealed that Amur tiger DRB alleles clustered with those from other felid species, supporting trans-species polymorphism. These results indicate that the DRB gene in Amur tigers exhibits a high degree of polymorphism, and that DRB*02 may be a susceptibility gene for E. bieneusi.
Ethyl acetate extract from Dinizia excelsa Ducke wood: A potential phytotherapeutic agent with antioxidant, cytotoxic and hemolytic (in normal cells), immunomodulatory, antimicrobial, antiparasitic and antitumor activities.
Dos Anjos Santos CÁ, Pereira AVLA, Dos Santos KCC … +8 more , da Silva AFF, de Oliveira Queirós ME, de Oliveira Moraes Miranda JF, Brayner FA, Alves LC, Marques DSC, de Lima MDCA, da Cruz Filho IJ
Mol Biochem Parasitol · 2026 Jun · PMID 42259421 · Publisher ↗
Amazonian biodiversity is an underexploited source of bioactive natural products with potential relevance to drug discovery for neglected diseases. Here, we characterized the chemistry and multi-target in vitro activity...
Amazonian biodiversity is an underexploited source of bioactive natural products with potential relevance to drug discovery for neglected diseases. Here, we characterized the chemistry and multi-target in vitro activity of an ethyl acetate extract from Dinizia excelsa wood. Extraction yielded 4.84 ± 0.10% and produced a phenolic-rich fraction with high total phenolics (501.8 ± 1.0 mg GAE/g extract), flavonoids (172.4 ± 0.8 mg QE/g), flavonols (49.7 ± 0.3 mg QE/g), and hydrolyzable tannins (229.4 ± 1.2 mg TAE/g). LC-HRMS dereplication annotated 19 metabolites, dominated by glycosylated flavonoids (rutin, isoquercetin), phenolic acids (ferulic and ellagic acids), ellagic derivatives (urolithins), and galloylated hydrolyzable tannins. The extract showed moderate-to-low antioxidant capacity across complementary assays (IC₅₀ 78.38-161.99 µg/mL) and a favorable safety profile, with moderate/low cytotoxicity in mammalian cell lines (IC₅₀ 364-700 µg/mL) and minimal hemolysis (<6% up to 1000 µg/mL). In murine splenocytes, the extract preserved membrane integrity, induced dose-dependent proliferation, and promoted a broad but controlled cytokine response (↑IL-2, IL-4, IL-10, IL-12, IFN-γ, IL-17, TNF-α; regulated TGF-β), alongside reduced NO, mild cytosolic ROS modulation, and stable mitochondrial membrane potential. Notably, it displayed strong antiparasitic activity against Trypanosoma cruzi (IC₅₀ 2.37-3.94 µg/mL) and Leishmania spp. (IC₅₀ 1.83-6.43 µg/mL), with additional activity against Schistosoma mansoni (IC₅₀ 114.83-247.0 µg/mL) and Plasmodium falciparum 3D7 (IC₅₀ 5438.27 ng/mL). Antibacterial MICs ranged 16-512 µg/mL and antifungal MICs 16-256 µg/mL, consistent with bacteriostatic/fungistatic effects.
Plasmodium falciparum invasion ligand gene transcript profiles in different populations.
Lantero-Escolar E, Stewart LB, Singh B … +3 more , Claessens A, Amambua-Ngwa A, Conway DJ
Mol Biochem Parasitol · 2026 May · PMID 42190989 · Publisher ↗
Plasmodium falciparum merozoites invade erythrocytes using various ligand-receptor interactions. Important ligands encoded by the eba and Rh gene families have varying expression levels in different parasite isolates, af...
Plasmodium falciparum merozoites invade erythrocytes using various ligand-receptor interactions. Important ligands encoded by the eba and Rh gene families have varying expression levels in different parasite isolates, affecting their vaccine candidacy. Analyses of clinical isolates from endemic areas in Africa have indicated that most variation in these expression profiles exists within each local area, and only minor differences are seen between areas, although comparisons with non-African populations have not previously been performed. To enable this, relative transcript levels of three eba genes and five Rh genes have been analysed in new population samples, Malaysian isolates sampled from Sabah State in Borneo prior to endemic malaria elimination, and Gambian isolates, cultured under the same conditions to harvest schizonts for reverse transcription quantitative PCR assays. Significant differences between these populations were seen for three of the ligand genes, levels of eba175 being higher in Malaysia, while levels of eba181 and Rh2b were lower in Malaysia. The variation in gene transcript profiles was not associated with having single or multiple genotypes within each isolate. The distinctness of the Malaysian population expression profile was also supported by comparing previous data on clinical isolates from Ghana. In tests for correlation with previously determined parasite multiplication rates, eba181 transcript levels correlated positively among Malaysian isolates but not among Gambian isolates. These findings suggest that expression of three P. falciparum merozoite ligands involved in invasion may be regionally differentiated, and further analysis of Asian parasite populations would be important if vaccines based on these candidates are to be considered for future use.
Exploring the Warburg effect in Chagas disease: A biochemical approach to metabolic reprogramming.
Santos CV, Zandona VP, Bonamin F … +2 more , Chagas EFB, Martins LPA
Mol Biochem Parasitol · 2026 May · PMID 42167494 · Publisher ↗
Chagas disease (CD), caused by Trypanosoma cruzi, is a significant problem of public health. The infection induces inflammatory processes in tissues, leading to metabolic changes similar to the Warburg Effect (WE). To ev...
Chagas disease (CD), caused by Trypanosoma cruzi, is a significant problem of public health. The infection induces inflammatory processes in tissues, leading to metabolic changes similar to the Warburg Effect (WE). To evaluate the presence of WE during the progression of CD in mice, 72 male Swiss mice were divided in two groups: one group with 36 mice was infected with 5.0 × 10⁴ trypomastigote forms of T. cruzi QM2 strain, and another group with 36 mice was the control. Every week the mice were weighed, glycemia was measured and lactate was determined biweekly. At the end of each experimental period: 30, 60 and 120 days post-infection, the animals were euthanized for blood collection to analyze TBARS, LDH, urea, creatinine, PCR, pO and pCO. Parasitemic peak was reached in 17th day, when blood glucose was lowered. Glycemia was significantly lower in the infected group, with high lactate dehydrogenase (LDH) activity, suggesting the occurrence of WE, despite normal lactate and pH levels in this group. Neither TBARS nor C-reactive protein showed significant difference across the groups studied. Urea levels did not show significant differences between the groups, but the decrease in its concentration in the infected group may be due to the use of its precursors for the production of nitric oxide. It is concluded that hypoglycemia and increased LDH activity during the acute phase of CD led to a metabolic shift towards glycolysis, suggesting the presence of WE. Further studies are necessary to validate this metabolic shift in CD.
Stage-specific differential gene expression leads to adaptive changes in the promastigote and amastigote stages of Leishmania donovani.
Jha I, Tiwary BK
Mol Biochem Parasitol · 2026 May · PMID 42150675 · Publisher ↗
Leishmania donovani exists in two distinct environments to complete its life cycle. It exists as a non-motile infective amastigote state in humans and as a motile promastigote state in the sandfly gut. Although the diffe...
Leishmania donovani exists in two distinct environments to complete its life cycle. It exists as a non-motile infective amastigote state in humans and as a motile promastigote state in the sandfly gut. Although the differences in gene expression between life-cycle stages have been extensively studied, the contribution of variability of gene expression to parasite adaptation remains poorly understood. Here, we have explored transcriptional changes in L. donovani using bulk RNA-seq data, using the amastigote as a reference. After the differential expression analysis, we calculated the gene-wise Wasserstein distance to capture shifts in the expression distribution across the stages. We found that amastigotes show overall lower transcriptional changes than promastigotes, but greater heterogeneity in genes related to stress responses, membrane proteins, and regulation. Importantly, we identified a subset of genes exhibiting high distributional shifts despite minimal changes in mean expression, which were not detected by conventional differential expression analysis. This suggests that deeper regulatory mechanisms may be masked by mean-based differential expression analyses. Furthermore, the poorly annotated genes in both stages were annotated, and many were found to have specific roles that help the parasite survive within host cells and vectors. Overall, our results provide exploratory insights into gene expression variability, revealing genes with stable mean expression but altered distributional patterns across life stages of L. donovani. Together, these findings suggest that transcriptional heterogeneity may constitute an underappreciated regulatory layer that contributes to parasite adaptation during the transition between vector and host environments.
De-novo discovery of posttranslational histone modifications in Schistosoma mansoni stages.
Costa GG, Silva JPDL, Moreira LF … +14 more , da Silva Oliveira Teodoro C, Cruvinel GF, Gonçalves-Silva G, de Sousa Cardoso TC, de Araujo CB, de Lima LM, Correa SAP, do Amaral TD, do Patrocínio AB, Allegretti SM, de Souza Gomes M, de Castro Borges W, Grunau C, Cabral FJ
Mol Biochem Parasitol · 2026 May · PMID 42142712 · Publisher ↗
Schistosoma mansoni, a parasitic flatworm, causes schistosomiasis. Approximately 250 million people are infected and require drug treatment. Currently, Praziquantel is the only available drug, but it is ineffective again...
Schistosoma mansoni, a parasitic flatworm, causes schistosomiasis. Approximately 250 million people are infected and require drug treatment. Currently, Praziquantel is the only available drug, but it is ineffective against early infective stages. The development of new drugs is urgently needed. Posttranslational modifications (PTM) of histones are crucial for the parasite's life cycle, making them a suitable drug target. However, many of these modifications are conserved between humans and parasites, posing a risk of severe side effects for patients. Identifying schistosome-specific histone PTMs is essential. We employed a bottom-up mass spectrometry method combining first-time Data Independent Acquisition (DIA) and Data Dependent Acquisition (DDA) to quantify histone peptides and assess histone proteins across three S. mansoni stages. We selected 18 main post-translational modifications (PTMs) for peptide searches and identified 150 PTMs across peptides from H3, H4, H1/H5, and H2A of S. mansoni. We further refined with more stringency, given the complexity of the mass spectrometry data and our commitment to reliable data generation, we focused on quantifying H3 PTMs,which are well characterized in other species. For histone H3 PTMs, we identified peptides with high abundance and confidence: K27(1-methyl1-methyl)SAPATGGVK, K27(Dimethyl)SAPATGGVK, K9(acetyl)STGGK, and K9(Dimethyl)STGGK. Notably, both K27(Dimethyl)SAPATGGVK and K9(acetyl)STGGK showed higher abundance in schistosomula. Furthermore, we observed a positive correlation between the expression of the gene Smp_053140 and the abundance of the peptide K9(acetyl)STGGK in 3-day schistosomula. We then knocked down this gene, which affected schistosomula morphology, highlighting the significance of histone posttranslational modification and histone-modifying enzymes in S. mansoni development.
Probing the role of interfacial residues in the activity and structural stability of Adenylosuccinate lyase from Leishmania donovani.
Jigneshkumar A M, Jaykumar J, Anju P
Mol Biochem Parasitol · 2026 May · PMID 42142711 · Publisher ↗
Leishmania donovani ADSL is a tetrameric protein involved in the purine metabolism where the active site is formed from residues belonging to three different subunits. In this study, the amino acid residues- E334, N335 a...
Leishmania donovani ADSL is a tetrameric protein involved in the purine metabolism where the active site is formed from residues belonging to three different subunits. In this study, the amino acid residues- E334, N335 and R370 of LdADSL were studied for their contribution to the enzyme catalysis and inter-subunit binding. Mutating these residues resulted in reduced activity, stability and affinity towards the substrate, SAMP/AMP as shown by enzyme kinetics, fluorescence spectroscopy and thermal stability studies. MD simulation studies also supported this. Structural analysis points to disrupted interactions with the catalytic base, H196, reduced hydrogen bonds and electrostatic interactions between the substrate and the enzyme, C3-loop conformational changes and altered conformation of active site residues as reasons for reduced activity and stability. Incubation of pairs of the mutant enzymes restored partly the functional active site by subunit complementation. Our study highlighted the critical role of inter-subunit residues in maintaining both structural stability and proper active-site architecture in enzymes whose functional catalytic site is formed at interfaces of different subunits. This knowledge can be used to design more specific anti-leishmanials by targeting the inter-subunit interface of LdADSL.
Comparative transcriptomics suggests conserved mechanisms of anhydrobiosis in the entomopathogenic nematode Heterorhabditis indica.
Manimaran B, Jagannadham P, Parameshwaran C … +1 more , Mohan S
Mol Biochem Parasitol · 2026 May · PMID 42105871 · Publisher ↗
Anhydrobiosis is an evolutionarily conserved phenomenon observed across a diverse range of organisms. We have deployed a cross-species search to identify the homologs for anhydrobiosis-specific transcripts from Heterorha...
Anhydrobiosis is an evolutionarily conserved phenomenon observed across a diverse range of organisms. We have deployed a cross-species search to identify the homologs for anhydrobiosis-specific transcripts from Heterorhabditis indica. It revealed that H. indica transcriptome shares 14-53% homology with other EPNs, ∼27% with PPNs, ∼45% with Caenorhabditis elegans, and ∼6.5% with unrelated organisms like Drosophila melanogaster and Saccharomyces cerevisiae, which exhibit varying desiccation tolerance. Notably, the unfolded protein response (a prominent stress-related pathway) was shared across nematodes, indicating a conserved stress response mechanism regardless of the feeding behavior. We also performed the standalone BLASTx searches for the differentially expressed transcripts from anhydrobiotic H. indica against manually curated stress-specific protein databases like, DisProt, LEAPDB, HSPIR, sHSPdb, and DroughtDB. Significant matches were identified, with 15 upregulated transcripts in H. indica showing similarity against the DisProt database, 4 transcripts (2 upregulated and 2 downregulated) aligned with LEAPDB, 76 transcripts aligning with HSPIR, 14 with sHSPdb, and 76 with DroughtDB. The findings suggest that these homologs may perform analogous functions during anhydrobiosis in H. indica. Further, we characterized the intrinsically disordered proteins (IDPs) and late embryogenesis abundant (LEA) proteins using bioinformatic tools such as PONDR, localCIDER, and DEPP and found that the disorderness ranges from ∼ 8-100%. This study provides valuable insights into the molecular basis of anhydrobiosis and highlights conserved stress-response mechanisms that could inform broader applications in stress biology.
From Mystery to mechanism: The role of Base J in transcription termination and gene regulation in trypanosomatids and other kinetoplastids.
Watts E, Harris V, Smith TK
Mol Biochem Parasitol · 2026 May · PMID 42086123 · Publisher ↗
The modified nucleotide β-D-glucopyranosyloxymethyluracil (Base J) is found uniquely in kinetoplastids. Accumulating evidence has linked J to gene expression regulation, though its precise mechanistic role has remained e...
The modified nucleotide β-D-glucopyranosyloxymethyluracil (Base J) is found uniquely in kinetoplastids. Accumulating evidence has linked J to gene expression regulation, though its precise mechanistic role has remained elusive. Recent studies suggest J recruits chromatin restructuring and transcription termination complexes to DNA via a novel J-Binding Protein (JBP3), revealing diverse mechanism of J function. This review provides a comprehensive summary of Base J, exploring its biological roles and outlook as a parasite-specific therapeutic target. The necessity of functional J studies in species beyond Trypanosoma brucei will also be addressed, essential to uncover J functional divergence amongst kinetoplastids.
Preliminary in vitro evaluation of the immunomodulatory, schistosomicidal, antibacterial, antifungal, and antitumor activities of naphthyl-thiazole compounds.
Dos Santos KCC, Van Lauter Albuquerque Pereira A, Freire da Silva AF … +5 more , Brayner FA, Alves LC, Marques DSC, da Cruz Filho IJ, de Lima MDCA
Mol Biochem Parasitol · 2026 Jun · PMID 42082004 · Publisher ↗
The search for new compounds with multiple therapeutic actions is crucial to address public health challenges such as microbial and parasitic resistance, as well as cancer. In this context, this study evaluated the in vi...
The search for new compounds with multiple therapeutic actions is crucial to address public health challenges such as microbial and parasitic resistance, as well as cancer. In this context, this study evaluated the in vitro immunomodulatory, schistosomicidal, antimicrobial, and antitumor activities of 13 thiosemicarbazones (1a-m) and 16 thiazoles (2a-p). All compounds exhibited low cytotoxicity in murine splenocytes, maintaining cell viability above 95%. They significantly modulated markers of pro- and anti-inflammatory immune responses, increasing levels of IL-2, IL-4, IL-10, IFN-γ, mitochondrial and cytosolic reactive oxygen species (ROS), mitochondrial membrane potential, intracellular calcium concentration, and increasing CD4⁺ and CD8⁺ lymphocyte populations, while reducing nitric oxide production. Against Schistosoma mansoni, thiazoles demonstrated greater activity than thiosemicarbazones, particularly compound 2k (IC₅₀: 31.4 µM for juveniles, 30.1 µM for adults). In antimicrobial assays, moderate activity was observed, with MIC values ranging from 16 to 128 µg/mL against bacteria and fungi. In antitumor tests, thiazole derivatives demonstrated greater potency and selectivity than thiosemicarbazones (IC₅₀: 0.80-0.92 µM vs. 1.11-1.30 µM), particularly compounds 2 g and 2 f. These findings confirm the multi-target therapeutic potential of these compounds, supporting their candidacy for the development of drugs targeting infectious diseases and cancer.
Temperature-dependent changes in lipid composition of the cestode Schistocephalus solidus.
Borvinskaya EV, Fokina NN
Mol Biochem Parasitol · 2026 May · PMID 42082003 · Publisher ↗
This study investigated lipid dynamics in larvae and sexually mature Schistocephalus solidus, a cestode parasite that transitions between cold-blooded fish and warm-blooded avian hosts. The lipid content was analyzed in...
This study investigated lipid dynamics in larvae and sexually mature Schistocephalus solidus, a cestode parasite that transitions between cold-blooded fish and warm-blooded avian hosts. The lipid content was analyzed in relation to the environmental temperature and parasite developmental stage. A two-day incubation revealed that mature worms accumulate cholesterol esters, reflecting resource investment in egg production. The fatty acid composition of mature worms revealed increased proportions of stearic (18:0), linoleic (18:2n-6), gamma-linolenic (18:3n-6), and cetoleic (22:1n-11) acids, alongside a decrease in pentadecenoic (15:1) acid. The saturated-to-unsaturated fatty acid ratio remained stable, suggesting that no significant adjustments occurred in the membrane bilayers under thermal stress. The phospholipid composition shifted significantly, with a decrease in the phospholipid content and a marked increase in the phosphatidylinositol (PI) content in mature worms, indicating the activation of PI biosynthetic pathways. These findings highlight the strategic reallocation of resources in mature worms, prioritizing the accumulation of stored lipids over structural phospholipid synthesis. Additionally, the results suggest that specific lipid metabolism pathways in S. solidus are regulated by environmental temperature, providing insights into the adaptive strategies employed by this parasite during host transition.
Anti-inflammatory effects of valdecoxib found in Clonorchis sinensis excretory/secretory products in an Ankylosing Spondylitis.
Lee YJ, Kim MJ, Yu SM … +4 more , Cho J, Shim SC, Won EJ, Kim TJ
Mol Biochem Parasitol · 2026 Jun · PMID 42069184 · Publisher ↗
Clonorchis sinensis, a liver fluke, secretes immunomodulatory molecules that may suppress inflammation in autoimmune diseases such as ankylosing spondylitis (AS). However, the specific bioactive compounds involved remain...
Clonorchis sinensis, a liver fluke, secretes immunomodulatory molecules that may suppress inflammation in autoimmune diseases such as ankylosing spondylitis (AS). However, the specific bioactive compounds involved remain largely unidentified. We performed LC-MS/MS-based metabolomic profiling of CS-ESP and detected a compound identical to valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, as a candidate bioactive molecule. Then, we evaluated therapeutic efficacy of valdecoxib in curdlan-induced AS mice. Clinical arthritis scores, paw thickness, and joint histopathology were assessed. In vitro cytotoxicity was tested using an MTS assay in both RAW 264.7 cells and peripheral blood mononuclear cells (PBMCs) obtained from AS patients. Valdecoxib showed no significant cytotoxicity to RAW cells until at 15 μg/ml and to AS PBMCs until at 200 μg/ml, respectively. In the SKG mouse model, valdecoxib treatment effectively delayed the development of arthritis and significantly reduced its severity (clinical scores of disease control group vs. valdecoxib group, mean ± SEM; 5.28 ± 1.00 vs. 3.84 ± 1.08, p < 0.05). Histological evaluation showed reduced arthritis (Histopathology scores of the ankles, mean ± SD; negative control group vs. disease control group: 0.50 ± 0.45 vs. 9.33 ± 4.55, p < 0.001; disease control group vs. valdecoxib group: 9.33 ± 4.55 vs. 4.75 ± 0.76, p < 0.05) in mice treated with valdecoxib. The current study showed that a compound identical to valdecoxib detected in CS-ESP exhibited robust anti-inflammatory and joint-protective effects in an AS model and highlighted the need for investigation into the chemical identity and immunoregulatory mechanisms of CS-ESP metabolites.
Multifaceted antimalarial effects of curcumin: Targeting PfGSK3, cytokine modulation, and histological improvements.
Ali AH, Jamil SNH, Hassan WRM … +8 more , Agustar HK, Rizal SF, Datt LS, Embi N, Sidek HM, Basir R, Ling LY, Latip J
Mol Biochem Parasitol · 2026 Jun · PMID 42066911 · Publisher ↗
Curcumin, a polyphenolic compound exhibits various bioactivities, including antimalarial and anti-inflammatory effects. This study investigated the long-term antimalarial effects of curcumin through in vivo experiments u...
Curcumin, a polyphenolic compound exhibits various bioactivities, including antimalarial and anti-inflammatory effects. This study investigated the long-term antimalarial effects of curcumin through in vivo experiments using Plasmodium berghei NK65-infected mice, complemented by in vitro and in silico analyses targeting the plasmodial GSK3 protein. Through in vitro, the antimalarial activity of curcumin was assessed on P. falciparum K1 (multi-drug resistant strain) and 3D7 (sensitive strain) as well as P. knowlesi A1H1 of Plasmodium lactate dehydrogenase (pLDH) assay, alongside cytotoxic effects on Vero cells using the MTT assay. Curcumin demonstrated its bioactivity to disrupt the parasite's growth and replication based on the effective inhibition on both P. falciparum (3D7 EC=8.11 µM; K1 EC=31.21 µM) and P. knowlesi (EC=4.51 µM). Molecular docking studies explored curcumin's interaction with the ATP-binding pocket of P. falciparum glycogen synthase kinase-3 (PfGSK3) with favourable binding affinity (-8.72 kcal/mol), revealing it potential as a selective inhibitor. Further, in vivo experiments validated curcumin's immunomodulatory activities and therapeutic effects in P. berghei-infected mice. Prolonged curcumin treatment has shown to significantly reduce the parasitaemia compared to the controls. Cytokine profiling via ELISA showed enhanced levels of anti-inflammatory cytokines (IL-10, IL-4) and decreased pro-inflammatory markers (TNF-α, IFN-γ), mitigating systemic inflammation associated with malaria. Histopathological analysis revealed reduction of tissue damage in the curcumin-treated mice, including decreasing parasite sequestration, inflammatory cell infiltration, hepatocyte necrosis and hemorrhages. This study highlights curcumin's potentials in inhibiting PfGSK3, regulating immune responses, and attenuating tissue damage which support its therapeutic role against malarial infection.
Molecular detection of chloroquine resistance in Plasmodium vivax isolates from North India: Analysis of single nucleotide polymorphisms in pvmdr1 gene.
Nityadarshini N, Bir R, Biswas J … +3 more , Jadon RS, Mirdha BR, Verma N
Mol Biochem Parasitol · 2026 Jun · PMID 42034171 · Publisher ↗
OBJECTIVES: Plasmodium vivax remains a major cause of malaria in India, with chloroquine still used as first-line therapy. However, molecular data on resistance markers are limited. This study aimed to detect mutations i...
OBJECTIVES: Plasmodium vivax remains a major cause of malaria in India, with chloroquine still used as first-line therapy. However, molecular data on resistance markers are limited. This study aimed to detect mutations in the pvmdr1 gene of P. vivax isolates and to assess their potential role as markers of chloroquine resistance. METHODS: A total of 7530 patients with acute undifferentiated febrile illness were screened. Blood samples were examined using microscopy, rapid diagnostic tests, and PCR. Isolates positive for P. vivax mono-infection were subjected to PCR for pvmdr1 amplification followed by Sanger sequencing. Global pvmdr1 sequences from GenBank were included for phylogenetic analysis. RESULTS: Among 7530 patients, 75 (0.99%) were confirmed as P. vivax malaria. The mean age was 29.2 years, with a male-to-female ratio of 2:1. Fever with chills was present in all cases, while neurological symptoms (6.6%), jaundice (6.6%), and haematological abnormalities (10.6%) were less frequent. Of the 75 isolates, 36 were successfully sequenced. M908L and F1076L were present in 100% of isolates, while T898A was detected in 5.6%. Phylogenetic analysis showed clustering of Indian isolates with haplotypes from Madagascar and Afghanistan, whereas Brazilian haplotypes formed a distinct branch. CONCLUSIONS: This study detected the presence of pvmdr1 polymorphisms in P. vivax isolates from North India. Although M908L and F1076L mutations were fixed in all isolates, their role in clinical chloroquine resistance remains uncertain, particularly in the absence of Y976F. Continuous molecular surveillance, combined with therapeutic efficacy studies, is essential to monitor emerging resistance and guide malaria treatment policies.
Proteomic profiling of hydatid cyst fluid obtained in mouse strains exhibiting different susceptibility to secondary cystic echinococcosis.
Muniz-Lagos AC, Cucher M, González-Porcile MC … +2 more , Mourglia-Ettlin G, Miles S
Mol Biochem Parasitol · 2026 Jun · PMID 41962870 · Publisher ↗
Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato (s.l.), is a neglected tropical disease affecting over one million people worldwide. The proteomic composition of hydatid cyst fluid (HCF) varies d...
Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato (s.l.), is a neglected tropical disease affecting over one million people worldwide. The proteomic composition of hydatid cyst fluid (HCF) varies depending on the host species and cyst location, influencing its diagnostic potential; however, the impact of intra-species host genetic variation on HCF remains poorly understood. To address this, we conducted comparative proteomic analyses of HCF from experimental secondary CE in mouse strains differing in infection susceptibility: BALB/c, C57BL/6, and CD1. Nine HCF pools (three per strain) were analyzed using high-resolution nanoLC-MS/MS coupled to Orbitrap mass spectrometry. Across all samples, 466 distinct proteins were identified, including 204 and 262 of parasite and host origin, respectively. The HCF from CD1 mice exhibited a markedly distinct proteomic profile compared with BALB/c and C57BL/6, containing 401 core proteins versus 330 and 292, respectively. A shared set of 256 proteins was consistently detected across all strains, among which 58 showed significant differences in abundance; predominantly between CD1 and the inbred strains. Several host serpin family proteins varied notably in abundance among strains. These findings suggest that host genetic background may influence the composition and relative abundance of HCF proteins, particularly those related to immune function. The identification of invariant proteins across genetically diverse hosts supports their potential as reliable immunodiagnostic markers, while variable expression of parasite serpins is consistent with possible roles in host adaptation and disease progression, though further validation is warranted.
GenBank-derived global inventory of benzimidazole resistance markers in the Haemonchus contortus β-tubulin 1 gene.
Azeem A, Khan MK, Mehmood MS … +11 more , Abbas RZ, Ali S, Mughal MAS, Abbas Z, Afresham S, Latif M, Imran M, Sindhu ZUD, Ashraf MU, Usman M, Ahmed W
Mol Biochem Parasitol · 2026 Jun · PMID 41956133 · Publisher ↗
Haemonchus contortus is a highly pathogenic gastrointestinal nematode of ruminants and a major cause of production losses in small livestock systems. Its rapid life cycle and blood-feeding habit make it one of the most d...
Haemonchus contortus is a highly pathogenic gastrointestinal nematode of ruminants and a major cause of production losses in small livestock systems. Its rapid life cycle and blood-feeding habit make it one of the most damaging helminths affecting sheep and goats worldwide. Control relies mainly on anthelmintics, particularly benzimidazoles, macrocyclic lactones, and levamisole; however, resistance to these drug classes has become widespread. Benzimidazole resistance in H. contortus is strongly associated with mutations in the β-tubulin 1 gene, particularly at codons 167, 198, and 200. In this study, all publicly available H. contortus β-tubulin 1 sequences deposited in GenBank (n = 439) were compiled and screened for resistance-associated variants. Records were retrieved programmatically using Biopython and organized within a structured SQL/MariaDB database for downstream analysis. Multiple sequence alignment was performed using ClustalX and verified in BioEdit. After excluding sequences lacking complete coverage of the three target codons, 270 sequences were retained for analysis. Within this GenBank-derived dataset, 38.9% of analyzed sequences contained at least one resistance-associated substitution, reflecting the composition of available database records rather than true field prevalence. Double mutations were rare and no triple mutations were detected. Patterns observed within the available GenBank dataset showed variation across recorded collection years, countries, and host species. Among sequences with geographic metadata, resistant alleles were most frequently observed in records from Brazil and the United States, while many sequences lacked location or host information. Within the available GenBank dataset, host-associated summaries indicated higher proportions of resistance markers among sequences derived from goats and sheep compared with cattle and buffalo. These results provide a systematic overview of benzimidazole resistance markers present in publicly available H. contortus β-tubulin 1 sequences. Because GenBank submissions are not based on systematic field sampling, the observed patterns should be interpreted as database-derived summaries rather than estimates of true global prevalence.
Polygenic control of Rhipicephalus microplus infestation in purebred and crossbred cattle revealed by GWAS.
Simões MRS, Campos GS, Gomes CCG … +7 more , Milanesi M, Garcia JF, Camargo SS, Comin HB, Rossato ADP, Boligon AA, Cardoso FF
Mol Biochem Parasitol · 2026 Jun · PMID 41831245 · Publisher ↗
Selecting cattle for enhanced resistance to ticks is essential for improving herd productivity and safeguarding animal welfare. In Brazilian production systems, tick resistance is a key factor influencing competitiveness...
Selecting cattle for enhanced resistance to ticks is essential for improving herd productivity and safeguarding animal welfare. In Brazilian production systems, tick resistance is a key factor influencing competitiveness in domestic and export-oriented beef chains. This study evaluated tick resistance in taurine and indicine cattle and their crossbreds in Rio Grande do Sul, a subtropical region where Rhipicephalus (Boophilus) microplus infestation is highly prevalent and represents the only tick species parasitizing cattle. Breed-group differences in tick counts were quantified, and the potential of genomic tools to support the selection of more resistant animals was assessed. A repeated-measures mixed model was used to compare mean tick loads and to estimate direct, maternal, and heterotic effects. Nellore cattle exhibited the lowest mean tick counts (1.00 ± 0.24), followed by Angus × Nellore (3.66 ± 0.57), Nellore × Angus (4.34 ± 0.55), Caracu × Angus (8.24 ± 0.78), Angus (10.28 ± 0.94), Angus × Hereford (12.44 ± 1.37), Hereford (12.61 ± 1.38), and Hereford × Angus (12.92 ± 1.18). Heritability and repeatability for tick infestation were 0.165 ± 0.03 and 0.179 ± 0.05, respectively. A genome-wide association study identified genomic regions on chromosomes 3, 4, 5, 16, and 22 associated with variation in tick load. Candidate genes within these regions were characterized using MeSH enrichment analyses. The results reinforce the polygenic basis of tick resistance and demonstrate the relevance of genomic information for improving selection strategies in both purebred and crossbred cattle populations.
Knockdown resistance in mosquito vectors: Molecular mechanisms, global spread, and future directions for sustainable vector control.
Godson SGA
Mol Biochem Parasitol · 2026 Jun · PMID 41825782 · Publisher ↗
Pyrethroid insecticides remain central to malaria and dengue vector control programmes. However, their long-term effectiveness is increasingly threatened by knockdown resistance (kdr). kdr arises from mutations in the vo...
Pyrethroid insecticides remain central to malaria and dengue vector control programmes. However, their long-term effectiveness is increasingly threatened by knockdown resistance (kdr). kdr arises from mutations in the voltage-gated sodium channel (VGSC) gene, particularly within the IIS6 and IIIS6 domains, which reduce insecticide binding while preserving normal neuronal function. Key mutations include L1014 substitutions in Anopheles species and V1016 and F1534 variants in Aedes species. These mutations have evolved independently across multiple endemic regions under sustained insecticide pressure. This review integrates molecular, functional, evolutionary, and operational evidence to examine how kdr is reshaping contemporary vector control. It summarizes global trends in allele frequency changes, findings from electrophysiological and genome-editing studies confirming causal mechanisms, and multilocus analyses demonstrating progressive resistance intensification. Particular emphasis is placed on the interaction between target-site mutations and metabolic detoxification pathways, which together amplify resistance intensity and complicate genotype-phenotype interpretation. The review further discusses surveillance strategies, evidence-based thresholds for insecticide switching, the role of synergist-enhanced formulations, alternative chemical classes, and integrated vector management approaches. Emerging genetic technologies, including CRISPR-based editing and gene drive systems, are evaluated within realistic regulatory and ecological frameworks. By linking molecular mechanisms with field performance and programme-level decision-making, this synthesis positions kdr not merely as a mutation class but as a dynamic indicator of selective pressure and intervention sustainability in mosquito-borne disease control.
Characterisation of Encephalitozoon cuniculi α-actinin.
Sandblad L, Backman L
Mol Biochem Parasitol · 2026 Jun · PMID 41730339 · Publisher ↗
The Encephaliozoon cuniculi is an obligate intracellular microsporidian parasite with a highly reduced genome, yet it contains several key components of an actin cytoskeleton. In this study, we characterise the α-actinin...
The Encephaliozoon cuniculi is an obligate intracellular microsporidian parasite with a highly reduced genome, yet it contains several key components of an actin cytoskeleton. In this study, we characterise the α-actinin-like protein from the parasite to gain insight into its role in actin organisation. The protein contains three domains typical of α-actinins: an N-terminal actin-binding domain and a C-terminal calmodulin-like domain, separated by a rod domain. Gel filtration analysis demonstrated that the recombinant protein formed stable dimers, consistent with the canonical antiparallel α-actinin structure. Actin co-sedimentation assays and electron microscopy confirmed that the α-actinin-like protein binds and cross-links actin filaments into tight bundles, whereas the isolated actin-binding domain binds but does not cross-link filaments. AlphaFold modelling predicted an overall structural arrangement compatible with an antiparallel dimer. Our results identify the E. cuniculi α-actinin-like protein as a true α-actinin homologue. The presence of actin-binding proteins in E. cuniculi as well as in other microsporidia with very small genomes implies that an actin-based cytoskeleton is important for their survival.
Characterisation of potential vaccine targets in Haemonchus contortus.
Bouchet C, Knight J, Cleland S … +2 more , Grant W, Umair S
Mol Biochem Parasitol · 2026 Jun · PMID 41724270 · Publisher ↗
In a recent study, bioinformatics and RNA interference (RNAi) were used to look for the genes responsible for the acute lethal or developmental arrest in Haemonchus contortus. Out of the fifty-six H. contortus genes sele...
In a recent study, bioinformatics and RNA interference (RNAi) were used to look for the genes responsible for the acute lethal or developmental arrest in Haemonchus contortus. Out of the fifty-six H. contortus genes selected as potential targets, 41 provided strong to moderate phenotype. Seven genes were then selected for expression, purification and characterisation in the present study. A 981 bp full-length cDNA encoding H. contortus fatty acid synthase thioesterase domain (HcFAS-TE) was cloned, expressed in Escherichia coli, and the recombinant protein purified and biochemically characterised. The protein sequence of HcFAS-TE showed the greatest similarity with FAS-TE of Teladorsagia circumcincta and Ancylostoma caninum. The optimum substrate concentration for recombinant HcFAS-TE was 125 µM, whereas the addition of 150 µM Orlistat reduced the HcFAS-TE activity by 85 %. A 1563 bp full-length aspartyl tRNA synthetase (HcDRS-1), a 3048 bp full-length glutamyl tRNA synthetase (HcERS-2), a 1482 bp vacuolar ATPase subunit A (HcVHA-12), a 1362 bp transcriptional co-activator histone acetyltransferase domain (HcCBP-1) and a 1362 bp full-length serum glucocorticoid-inducible kinase (HcSGK-1) and a 1152 bp full-length NADH-dependent oxidoreductase (HcF36A2.3) were also cloned, expressed in E. coli and purified. Despite varying assay conditions, there were no detectable activities for HcDRS-1, HcERS-2 or HcF36A2.3. Due to the assay complexity, no attempts were made to assay HcSGK-1 or HcVHA-12. Antibodies in serum and saliva from field-immune, but not parasite-naïve, animals recognised recombinant HcFAS-TE, HcVHA-12, HcCBP-1, HcF36A2.3, HcDRS-1, and HcERS-2, but not HcSGK-1, showing that an immune host has developed a response against the proteins.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe