Molecular And Biochemical Parasitology[JOURNAL]
Sun
200 papers
Structural characterization of glycolytic enzymes from Trypanosoma cruzi.
Austin K, Obakachi VA, Muzenda FL … +13 more , Moetlediwa MT, Agyei C, Craig T, Abendroth J, Edwards T, Nguyen M, Tran N, Staker BL, Subramanian S, Myler PJ, Zininga T, Govender KK, Chakafana G
Mol Biochem Parasitol · 2026 Jun · PMID 41713750 · Publisher ↗
Trypanosoma cruzi, the etiological agent of Chagas disease, depends on glycolysis for ATP production, rendering its glycolytic enzymes attractive targets for therapeutic development. Here, we report the high-resolution c...
Trypanosoma cruzi, the etiological agent of Chagas disease, depends on glycolysis for ATP production, rendering its glycolytic enzymes attractive targets for therapeutic development. Here, we report the high-resolution crystal structures of two essential glycolytic enzymes, glucose-6-phosphate isomerase (Tc PGI, 1.8 Å) and enolase (Tc enolase, 2.4 Å) and provide structural and computational analyses to support structure-based drug design. Tc PGI adopts a dimeric αβα sandwich fold and features a parasite-specific 53-residue N-terminal extension and a unique C-terminal hook region which both distinguish it from its human ortholog. Tc enolase exhibits the conserved (α/β) 8 TIM barrel fold but harbors minor distinct structural deviations, including an extended α17 helix and a structured α1 region, which differentiate it from human isoforms. Both enzymes exhibited high thermal stability, consistent with adaptation to the parasite's complex life cycle. Structure-based virtual screening using a scaffold with known multi-target potential identified distinct high-affinity inhibitors for each enzyme. Molecular dynamics simulations further confirmed stable enzyme-inhibitor interactions and favorable binding energetics. Collectively, these findings reveal structural signatures unique to T. cruzi glycolytic enzymes and lay the groundwork for the development of antiparasitic therapeutics.
In vitro and in silico evaluation of plant compounds as inhibitors of glutathione S-transferase from Rhipicephalus microplus and R. decoloratus.
Dos Santos Bezerra WA, da Rocha CQ, da Silva Vaz Junior I … +3 more , Ullah S, de Azevedo Junior WF, Soares AMDS
Mol Biochem Parasitol · 2026 Jun · PMID 41611097 · Publisher ↗
Ticks are widely distributed ectoparasites that transmit several pathogens and cause significant losses in livestock production. Resistance to commercial acaricides has become increasingly common, stimulating the search...
Ticks are widely distributed ectoparasites that transmit several pathogens and cause significant losses in livestock production. Resistance to commercial acaricides has become increasingly common, stimulating the search for new molecules with potential for tick control. Among possible targets, glutathione S-transferases (GSTs) play a central role in detoxification processes and are therefore attractive candidates for overcoming acaricide resistance. In this work, the inhibitory activity of plant compounds on recombinant GSTs from Rhipicephalus microplus (rGST-Rm) and R. decoloratus (rGST-Rd) was examined using in vitro and in silico approaches. Compounds tested included 3β-stearioxy-olean-12-ene, diosgenin, quercitrin, naringenin, ellagic acid, rutin, and quercetin, which belong to different chemical classes, including triterpenes, steroids, polyphenols, and flavonoids. In vitro assays showed that 3β-stearioxy-olean-12-ene and naringenin inhibited rGST-Rm with IC₅₀ values of 148.2 μM and 160.7 μM, respectively. For rGST-Rd, inhibition by quercitrin (IC₅₀ = 37.7 μM), naringenin (IC₅₀ = 177.7 μM), and rutin (IC₅₀ = 115.0 μM) was observed. Docking analyses predicted interactions between these molecules and tick GSTs. Overall, the results support the potential of GST inhibition as a strategy for acaricide development and indicate that some plant compounds may serve as starting points for future tick control methods.
Exploring the potential role of Opisthorchis felineus infection in cholangiocarcinogenesis.
Jain S
Mol Biochem Parasitol · 2026 Jun · PMID 41587590 · Publisher ↗
The relationship between the liver fluke, Opisthorchis felineus (Of) and cholangiocarcinoma (CCA) has been assessed by a limited number of studies. In the case of animal models, such studies have pointed towards a causal...
The relationship between the liver fluke, Opisthorchis felineus (Of) and cholangiocarcinoma (CCA) has been assessed by a limited number of studies. In the case of animal models, such studies have pointed towards a causal association between Of infection and CCA. As per these studies, Of has the ability to interfere with DNA excision repair systems through the generation of reactive oxygen and nitrogen species. It can also cause accumulation of by-products generated via lipid peroxidation and is also involved in the production of oxysterol like compounds, hence possess the ability to mutate different genes. Although chalangiocarcinogenis through Of infection in humans is not established, but hospital based studies, case studies and case-controlled studies as well as the analysis of medical statistics, especially from Russian Federation, point towards a strong correlation between them. The aim of this work is to present the current understanding of the association between Of and CCA. On the basis of available studies, this work identifies an array of factors linked with Of infection, which have been independently identified as cancer inducers in various other studies. These factors point towards a possible causative link between Of infection and CCA induction in humans but this observation warrants for more epidemiological, clinical and pathological studies to conclusively state Of to be a CCA inducer in humans. However, Of infection, which is currently placed in group 3 of IARC classification for CCA should be re-classified to a higher group of cancer inducers.
Isolation and characterization of a novel glutamate-gated chloride channel subunit (GLC-2) from the canine heartworm Dirofilaria immitis.
Nichols J, Forrester SG
Mol Biochem Parasitol · 2026 Jun · PMID 41581768 · Publisher ↗
Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Current heartworm treatment options include melarsomine chloridrate (an arsenical) to treat adult parasites and the macrocyclic lacton...
Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Current heartworm treatment options include melarsomine chloridrate (an arsenical) to treat adult parasites and the macrocyclic lactones. Unfortunately, resistance to macrocyclic lactones is emerging which is highlighting the need for the discovery of new anthelmintics. Cys-loop ligand-gated ion channels are an untapped source for novel drug targets essential for nematode neurotransmission. This work presents the isolation and preliminary pharmacological characterization of a glutamate-gated chloride channel, GLC-2, from D. immitis. Expression levels of GLC-2, identified in the adult female, adult male and microfilaria (Mf) life stages, were measured via qPCR, with highest expression found in the adult stages. Dim-GLC-2 forms homomeric channels with low sensitivity to monosodium L-glutamate (MSG) and L-glutamic acid. Homodimer models were created to visualize docking of glutamate to the binding site, and several potential interactions were identified and compared to the original crystal structure of the glutamate-gated chloride channel from Caenorhabditis elegans.
Multifunctional glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of parasites.
Mishra P, Joshi P
Mol Biochem Parasitol · 2026 Jun · PMID 41581767 · Publisher ↗
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme involved in glycolysis. However, non-glycolytic activities of this enzyme were subsequently discovered including DNA repair, cell death, membrane fusion and t...
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme involved in glycolysis. However, non-glycolytic activities of this enzyme were subsequently discovered including DNA repair, cell death, membrane fusion and transport. Recent studies have identified additional functions of this enzyme in parasites such as modulating host immune responses. For example, Haemonchus contortus GAPDH binds to complement C3 and also interacts with peripheral blood mononuclear cells. The enzyme from Leishmania major inhibits TNF-α production in host macrophages. Further, GAPDH of Schistosoma bovis, Dirofilaria immitis and Babesia microti binds to plasminogen that may facilitate parasite migration by preventing clot formation in its vicinity. Trichomonas vaginalis GAPDH interacts with many extracellular matrix proteins that may support initial adhesion of the organism to the host tissues. Surface associated GAPDH of Plasmodium berghei interacts with CD68 of Kupffer cells; a prerequisite for hepatocyte infection. This review discusses the general features of the enzyme and its significance in host-parasite relationships.
The first mitochondrial genome sequence and phylogenetic analysis of Clinostomum piscidium (Platyhelminthes: Clinostomidae): A first representative from India.
Chaudhary A, Ghosh D, Haldar A … +5 more , Narasimhan G, Baliyan R, Singh S, Sharma B, Singh HS
Mol Biochem Parasitol · 2026 Jun · PMID 41581766 · Publisher ↗
The digenean Clinostomum piscidium collected from the banded gourami (Trichogaster fasciata Bloch and Schneider, 1801) in India was morphologically identified, and the mitogenome was sequenced. Our results demonstrate th...
The digenean Clinostomum piscidium collected from the banded gourami (Trichogaster fasciata Bloch and Schneider, 1801) in India was morphologically identified, and the mitogenome was sequenced. Our results demonstrate that the parasite mitogenome is 14,318 bp long and consists of 12 protein-coding genes, 22 tRNA genes, two rRNA genes, and two non-coding control regions. Nucleotide skewness of the mt genome did not differ so much from other congeners. To date, the complete mitochondrial (mt) genome is available for only two Clinostomum species, Clinostomum complanatum and Clinostomum sinensis. Clinostomum piscidium exhibits a similar reorganization of the genome in comparison to all other sequenced Clinostomum species mt genomes except for the NCRs. The non-coding regions, the short NCR (SNCR) and long NCR (LNCR) are present and located between trnE and trnG and nad5 and trnE, respectively, in the C. piscidium genome. This is the first report on the mitogenome of Clinostomum sp. from India. The results provide data for further studies of the taxonomy and systematics of Clinostomum spp. It also advances Clinostomum mitochondrial genome resources, and thus offers imperative insights into the taxonomy and species identification of this genus.
Ivermectin localization at the amphidial pore and dye-filling defects in the IVR-10 strain of Caenorhabditis elegans.
Chaudhry U, Ashraf M, Ashraf S … +4 more , Ashraf M, Ashraf S, Raza A, Ashraf S
Mol Biochem Parasitol · 2026 Feb · PMID 41544910 · Publisher ↗
Amphids are sensory neurons that nematodes use to sense their environment. The IVR-10 strain is an ivermectin (IVM) resistant strain of Caenorhabditis elegans generated in the laboratory by repeated exposure to IVM. We f...
Amphids are sensory neurons that nematodes use to sense their environment. The IVR-10 strain is an ivermectin (IVM) resistant strain of Caenorhabditis elegans generated in the laboratory by repeated exposure to IVM. We found that the IVR-10 strain is dye filling defective which may be due to shortened amphids. The amphidial pore of the N2 Bristol strain lit up with an IVM antibody, providing direct immunolocalization of IVM and confirming early hypothesis based on functional studies. This suggests that IVM may enter the worms via the amphidial pore. The findings reiterate the importance of amphidial pore as a structure that is exposed to the chemical environment and may be a portal for drug entry.
Petasis-amide coupling enabled microwave-assisted synthesis of bis-benzothiazoles with safety profiling and antiprotozoal evaluation.
Gamit AS, Humal TR, Desai PS … +5 more , Patel NB, Moreno-Rodriguez A, Rivera G, Shaikh FM, Patel VM
Mol Biochem Parasitol · 2026 Feb · PMID 41519203 · Publisher ↗
A series of amide-linked bis-benzothiazoles was synthesized using an efficient microwave-assisted strategy that integrates the Petasis multicomponent reaction with HATU-mediated amide coupling. The methodology enabled ra...
A series of amide-linked bis-benzothiazoles was synthesized using an efficient microwave-assisted strategy that integrates the Petasis multicomponent reaction with HATU-mediated amide coupling. The methodology enabled rapid reactions (2 and 5 min) with high isolated yields of up to 94 %, highlighting the operational simplicity and energy efficiency of microwave-assisted organic synthesis. The structures of synthesized compounds were confirmed by FT-IR, H and C NMR, and ESI-MS spectroscopy. In vitro safety profiling against J774.2 macrophages demonstrated low cytotoxicity for most derivatives (CC > 200 µM). Antiprotozoal evaluation revealed notable activity against Leishmania mexicana, with compound 4a (IC = 12.40 µM) and compound 5a (IC = 27.05 µM) showing the highest potency, along with potent to good inhibition of Trypanosoma cruzi by compounds 5b and 5 g (IC = 58.95 and 51.89 µM, respectively). Structure-activity relationship analysis indicated that electron-donating substituents (-CH, -OCH3) on the amide moiety reduced cytotoxicity while enhancing antiprotozoal activity. In particular, compounds 5a, 5b, and 5 g emerged as promising lead candidates with a favourable balance between potency and safety for further development as antiprotozoal agents.
Lipid transport proteins in Toxocara canis: Host lipid acquisition and immune modulation.
Abou-El-Naga IF
Mol Biochem Parasitol · 2026 Feb · PMID 41429193 · Publisher ↗
Toxocara canis is unable to synthesize sufficient lipids de novo to meet its biological requirements and therefore depends on host-derived lipids for survival. The parasite expresses a diverse set of lipid transport prot...
Toxocara canis is unable to synthesize sufficient lipids de novo to meet its biological requirements and therefore depends on host-derived lipids for survival. The parasite expresses a diverse set of lipid transport proteins spanning all major classes, such as pseudocoelomic fluid lipoproteins (vitellogenins), nematode polyprotein antigens/allergens, intracellular carriers (fatty-acid binding proteins, phosphatidylinositol-transfer proteins), secreted lipid-binding proteins (fatty acid-and retinol-binding proteins, venom allergen-like proteins), membrane-associated transporters (Niemann-Pick C, ABC transporters, microsomal triglyceride transfer protein, bridge-like lipid-transfer proteins) and lipid-anchored carriers (phosphatidylethanolamine-binding proteins). These proteins mediate uptake and distribution of dietary and host lipids to drive parasite growth and reproduction, while simultaneously modulating host immune responses. Many of these transporters are released in the parasite's excretory/secretory products and are found in extracellular vesicles, where they mediate host-parasite interactions and immunomodulation. These specialized lipid-acquisition strategies support parasite survival, drive immune evasion and pathogenesis, and highlight these proteins as candidates for novel diagnostics or therapeutic targets.
Molecular identification of Aelurostrongylus abstrusus, Troglostrongylus brevior and Angiostrongylus chabaudi in domestic cats from the Azores Islands (Portugal).
Teixeira R, Valério-Bolas A, Flor I … +3 more , Pinto C, de Carvalho LM, Pomba MC
Mol Biochem Parasitol · 2026 Feb · PMID 41429192 · Publisher ↗
Domestic cats can be infected with various cardiopulmonary metastrongylids. Although A. abstrusus is widely distributed globally, data regarding the occurrence of T. brevior and A. chaubaudi in Portugal are currently non...
Domestic cats can be infected with various cardiopulmonary metastrongylids. Although A. abstrusus is widely distributed globally, data regarding the occurrence of T. brevior and A. chaubaudi in Portugal are currently nonexistent. This study aimed to evaluate the presence of cardiopulmonary parasite species in domestic cats from the Azores, Portugal, using copromicroscopy and molecular methods. A total of 57 domestic cats were included in this study, and fecal samples were previously analyzed using the Baermann technique. The detected larvae were collected, morphologically identified, and subsequently confirmed through molecular analysis using triplex semi-nested PCR. 57 domestic cats tested positive for cardiopulmonary parasites by copromicroscopy. Triplex semi-nested PCR analysis confirmed the presence of A. abstrusus (326 bp), T. brevior (520 bp) and A. chabaudi (200 bp) in the Azores archipelago. The present study is the first to molecularly confirm A. abstrusus, T. brevior, and A. chabaudi in domestic cats from Portugal and the first molecular report of domestic cats from the Azores Islands. Future studies are recommended to further investigate the distribution and epidemiology of these parasites in felines.
Potential synergistic antifungal activity of microbially synthesized silver nanoparticles and vitamin D against Candida albicans: In vitro and Galleria mellonella model studies.
Saberi Moqaddam Z, Khodavandi P, Khodavandi A … +1 more , Alizadeh F
Mol Biochem Parasitol · 2025 Dec · PMID 41391001 · Publisher ↗
Candida albicans poses a serious health threat, contributing to approximately 1.5 million deaths each year. Although azole drugs have been used to manage this pathogen, their effectiveness has been compromised by the eme...
Candida albicans poses a serious health threat, contributing to approximately 1.5 million deaths each year. Although azole drugs have been used to manage this pathogen, their effectiveness has been compromised by the emergence of drug-resistant strains. Therefore, silver nanoparticles (nano-Ag) and vitamin D are being explored as complementary rather than direct antifungal agents. The present study aims to investigate the effects of microbially synthesized nano-Ag alone and with vitamin D against fluconazole-susceptible and fluconazole-resistant C. albicans. The broth microdilution method, checkerboard microdilution assay, hyphal formation inhibition, and gene expression analysis of key virulence genes were performed on C. albicans treated with microbially synthesized nano-Ag, either alone or combined with vitamin D. Furthermore, the survival rate, haemocyte density, and microbial load in haemolymph were assessed in C. albicans-infected Galleria mellonella larvae after treatment with microbially synthesized nano-Ag alone and with vitamin D. The results demonstrated that microbially synthesized nano-Ag exhibited synergistic and additive interactions with vitamin D against C. albicans. This study also revealed that the combination of microbially synthesized nano-Ag and vitamin D effectively inhibited hyphal formation and significantly downregulated the expression of SAP and HWP1 genes in C. albicans. In vivo experiments further demonstrated that this combined treatment enhanced larval survival, increased haemocyte density, and reduced microbial load in the haemolymph. Taken together, these findings underscore the potential of microbially synthesized nano-Ag with vitamin D as a promising synergistic treatment for C. albicans infections, particularly those resistant to fluconazole.
LinfCul1 interaction with LinfSkp1 affects different cellular processes in Leishmania infantum.
Gomes E, Rolemberg Santana Travaglini Berti de Correia C, Torres C … +9 more , de Carvalho MC, de Oliveira de Castro T, Klaysson Pereira Regatieri W, Tamie Takamiya N, Rogerio LA, Cappellazzo Coelho A, Ide Aoki J, Regina Maruyama S, Roberti Teixeira F
Mol Biochem Parasitol · 2026 Feb · PMID 41371478 · Publisher ↗
LinfCul1 is a key component of the E3 ubiquitin ligase complex (LinfCRL1) in Leishmania infantum, which interacts with LinfSkp1 and LinfRbx1 at the N- and C-termini, respectively. To investigate the role of LinfCul1 in p...
LinfCul1 is a key component of the E3 ubiquitin ligase complex (LinfCRL1) in Leishmania infantum, which interacts with LinfSkp1 and LinfRbx1 at the N- and C-termini, respectively. To investigate the role of LinfCul1 in parasite proliferation, rosette formation, and macrophage infection, we generated a mutant LinfCul1 (mLinfCUL1) lacking the LinfSkp1 interaction region. Co-immunoprecipitation assays confirmed that mLinfCul1 exhibited reduced interaction with LinfSkp1, thereby disrupting LinfCRL1 function. Functional assays demonstrated that LinfCUL1 knockout (∆cul1) led to impaired proliferation and enhanced rosette formation, both of which were rescued by LinfCUL1 WT but not by mLinfCUL1 expression, confirming the requirement of the LinfCul1-LinfSkp1 interaction for these processes. Additionally, macrophage infection assays revealed that ∆cul1 parasites exhibited reduced infectivity and amastigote proliferation, which was restored upon LinfCUL1 WT expression in the parasites. Interestingly, mLinfCUL1 exhibited a lower infectivity index than ∆cul1, suggesting that LinfCul1 functions as a LinfCRL1 component that contributes to this process. These findings highlight the essential role of LinfCul1 in parasite proliferation and infectivity and reinforce its canonical function in ubiquitination-dependent parasite biology. Moreover, this study provides valuable insights into the molecular mechanisms governing parasite development and host interactions, thereby contributing to a better understanding of Leishmania infantum biology.
The efficacy and accuracy of ribosomal RNA depletion methods in the parasitic nematode Strongyloides ratti.
Ahmed M, Bishop C, Betancourt A … +2 more , Hunt V, Viney M
Mol Biochem Parasitol · 2026 Feb · PMID 41360346 · Publisher ↗
The depletion of ribosomal RNA (rRNA) is a critical step in RNA-sequence analyses, used to enhance the detection of non-rRNA molecules, such as messenger RNAs and non-coding RNAs. However, the efficiency and potential bi...
The depletion of ribosomal RNA (rRNA) is a critical step in RNA-sequence analyses, used to enhance the detection of non-rRNA molecules, such as messenger RNAs and non-coding RNAs. However, the efficiency and potential biases introduced by different rRNA depletion methods remain poorly characterized. Here, we evaluated three commercially available rRNA depletion kits - QIAseq FastSelect, riboPOOL, Zymo-Seq RiboFree - for their performance with the parasitic nematode Strongyloides ratti. We assessed the kits' efficiency in rRNA removal, the recovery of expressed genes and transposable elements, and the detection of spliced leader sequences and genes' operonic organization. Zymo-Seq demonstrated the highest sensitivity and minimal bias in a measure of gene expression, while QIAseq showed the least rRNA depletion and significant differential expression biases. Our findings underscore the importance of empirical validation of rRNA depletion methods, particularly for parasites and non-model organisms, and we suggest that Zymo-Seq as the optimal choice for S. ratti and related nematodes.
Green-synthesised ZnO-Ag-CuO nanocomposites from Thymus vulgaris and their in vitro anticoccidial activity.
Qadir RR, Mohammed HJ, Hamad SM … +2 more , Mirzaei Y, Ahmed MH
Mol Biochem Parasitol · 2025 Dec · PMID 41314352 · Publisher ↗
BACKGROUND: Coccidiosis is a significant parasitic disease affecting poultry, resulting in substantial economic losses due to its impact on growth, increased mortality, and compromised bird health. AIM: This study aimed...
BACKGROUND: Coccidiosis is a significant parasitic disease affecting poultry, resulting in substantial economic losses due to its impact on growth, increased mortality, and compromised bird health. AIM: This study aimed to evaluate the in vitro anticoccidial effects of a novel green-synthesised ZnO-Ag-CuO nanocomposite, using Thymus vulgaris extract. METHODS: The nanocomposite was synthesised through an eco-friendly method employing T. vulgaris as a stabilising and reducing agent. Characterisation was performed using UV-Vis spectroscopy, FTIR, XRD, SEM, and EDX, confirming its high crystallinity, nanoscale size, and the successful integration of ZnO, Ag, and CuO phases. Anticoccidial activity was assessed via a sporulation inhibition assay against Eimeria spp. Oocysts isolated from broiler chickens. RESULTS: The nanocomposite significantly reduced oocyst sporulation and increased the proportion of damaged and unpopulated oocysts in a dose-dependent manner (0.1-1 mg/mL) (p < 0.0001). ZnO-Ag-CuO NCs showed a dose-dependent anticoccidial effect, reducing sporulated oocysts to 56.41 %, 33.63 % and 22.9 % at 0.1, 0.5 and 1.0 mg/mL (control 88.62 %; p < 0.0001). Unsporulated oocysts increased to 15.9-62.22 % (control 13.33 %), while damaged oocysts reached up to 14.82 % (control 0 %). CONCLUSION: The green-synthesised ZnO-Ag-CuO nanocomposite demonstrated strong in vitro anticoccidial activity; however, further studies are needed to evaluate the nanocomposite's potential toxicity, formulation, stability under biological conditions, safety before practical applications and potential environmental impact within a One Health framework. FUTURE PLANS: In vivo studies are recommended to validate the efficacy and safety of these approaches for large-scale applications.
CRISPR-Cas systems: Pioneering next-generation diagnostic tools for parasitic diseases.
Verma R, Das G, H V M … +8 more , Muwel N, Choudhary R, Kumar S, Nath S, Gattani A, Gupta V, Sharma RK, Ajith Y
Mol Biochem Parasitol · 2025 Dec · PMID 41161575 · Publisher ↗
Parasitic diseases pose significant threats to both human and veterinary health, causing morbidity, mortality, and economic losses. Effective diagnostics are critical, yet conventional methods such as microscopy, serolog...
Parasitic diseases pose significant threats to both human and veterinary health, causing morbidity, mortality, and economic losses. Effective diagnostics are critical, yet conventional methods such as microscopy, serology, and polymerase chain reaction (PCR) are limited by low sensitivity, cross-reactivity, or dependence on costly equipment and skilled personnel. Isothermal amplification techniques, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), have improved point-of-care (POC) applications but remain limited by nonspecific amplification and reduced sensitivity for low-copy targets. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems have emerged as transformative tools in molecular diagnostics, offering high sensitivity, specificity, rapidity, and cost-effectiveness. This review presents an overview of CRISPR-Cas systems, their historical development, classification (Class 1 and Class 2, Types I-VI), molecular mechanisms, and diagnostic potential in parasitic diseases, with illustrative examples from studies published between 2017 and May 2025. Despite significant progress, CRISPR-based diagnostics face challenges such as off-target activity, dependence on nucleic acid amplification, and complex sample preparation. Future directions focus on amplification-free detection, multiplexed assay development, and integration with nanotechnology, microfluidics, smartphone-based devices, and artificial intelligence. CRISPR-Cas technologies thus represent a promising frontier in next-generation diagnostics for parasitic disease surveillance, control, and personalized healthcare in both human and veterinary health.
Proteomic analysis reveals differential responses to praziquantel in two Schistosoma mansoni strains with distinct phenotypes.
Valentini MB, Mendes TMF, Cabral FJ … +1 more , Allegretti SM
Mol Biochem Parasitol · 2025 Dec · PMID 41151641 · Publisher ↗
Different Schistosoma mansoni strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomi...
Different Schistosoma mansoni strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomic analysis to compare two strains of S. mansoni, Belo Horizonte (SmBH) and Sergipe (SmSE), which differ in phenotypic traits and susceptibility to praziquantel (PZQ). BALB/c mice were infected and treated with a sub-curative dose of PZQ (50 mg/kg) 45 days post-infection. Male and female worms were recovered 15 days after treatment, and pooled samples were processed for trypsin digestion and mass spectrometry. Over 1000 proteins were identified. No significant differences were observed in protein expression between untreated females of the two strains. In untreated males, 16 proteins showed differential expression: 11 upregulated in SmBH, mostly related to metabolic and energy production pathways, and 5 upregulated in SmSE. PZQ exposure did not significantly alter protein expression in SmBH worms. In contrast, SmSE males showed 74 differentially expressed proteins post-treatment, with 58 upregulated, including proteins with antioxidant and antiapoptotic functions commonly associated with drug resistance. SmSE females showed upregulation of three proteins after treatment, mostly related to cytoskeletal and muscular structure, suggesting less PZQ-induced damage. These results suggest that SmSE exhibits adaptive proteomic responses to PZQ-induced oxidative stress, which may contribute to its increased survival after treatment. Our findings provide molecular insight into strain-specific responses to PZQ and highlight potential mechanisms underlying reduced drug susceptibility in S. mansoni.
Can flukes cause cancer? Insight into molecular links between parasites and carcinogenesis.
Paluch M, Cudzik M, Kędra A … +5 more , Olszyna M, Dziura A, Jaskulska P, Król G, Kondziołka W
Mol Biochem Parasitol · 2025 Dec · PMID 41138780 · Publisher ↗
Cancer deaths are increasing year by year worldwide. Many factors contribute to the development of cancer, including genetic and epigenetic factors, as well as environmental factors such as diet, physical activity, stimu...
Cancer deaths are increasing year by year worldwide. Many factors contribute to the development of cancer, including genetic and epigenetic factors, as well as environmental factors such as diet, physical activity, stimulants (tobacco, alcohol), exposure to excessive UV radiation, stress, and infections. In recent years, many studies have shown a strong correlation between parasitic infections and the oncogenic process leading to the development of human cancers. Studies indicate an association between progressive inflammation, risk of infection, or bacterial/viral co-infection during parasitosis and oncogenesis. This article discusses six species of flukes listed by the International Agency for Research on Cancer (Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Opisthorchis viverrini, Clonorchis sinensis, and Opisthorchis felineus) for their carcinogenic potential, biology, and epidemiology. Particular attention was paid to the molecular mechanisms that are altered during fluke invasion, which ultimately lead to the development of neoplastic lesions in humans and animals.
Recent advancements in the diagnosis of parasitic diseases.
Afresham S, Khan MK, Mughal MAS … +10 more , Mehmood MS, Ali S, Bashir M, Abbas Z, Azeem A, Ahmed W, Imran M, Abbas RZ, Sindhu ZU, Sajid MS
Mol Biochem Parasitol · 2025 Dec · PMID 41138779 · Publisher ↗
Parasitic infections present a significant health risk to the public, affecting millions of people, particularly in underdeveloped and developing countries. In developing countries, these infections are also responsible...
Parasitic infections present a significant health risk to the public, affecting millions of people, particularly in underdeveloped and developing countries. In developing countries, these infections are also responsible for causing significant economic challenges due to elevated healthcare expenditure. Accurate diagnosis and effective treatment methods are essentially required to combat this global issue. For decades, traditional diagnostic methods such as microscopy, serological testing, histopathology, and culturing have been used for the diagnosis of these parasitic infections. While these methods can be effective and helpful in many ways, they often consume a lot of time, require an elevated level of expertise, and have limited applications particularly in endemic regions having issues like poor infrastructure and limited access to healthcare facilities. This review aims to highlight the urgent need for a revolution to replace these conventional techniques with more affordable, quick, and field-adjustable tools such as rapid diagnostic tests (RDTs) and molecular methods and provides a comprehensive picture of advanced diagnostic tools used in the identification of parasites. With the advancements in science and technology, molecular methods such as Polymerase chain reaction, Next generation sequencing, and isothermal loop-mediated amplification have remarkably enhanced the sensitivity and accuracy of parasite detection and identification. The range of these diagnostic methods has further extended by advanced serological methods, imaging techniques, and immunological methods. Moreover, the innovations in nanotechnology, CRISPR-Cas methods, and multi-omics techniques for identification of parasite DNA, antigens, metabolites, and host responses are invaluable for diagnostic accuracy, comprehensive understanding of parasite biology, and for the discovery of new therapeutic targets and diagnostic biomarkers. However, further research and developments are required for an effective and long-lasting impact of these advancements.
Targeted inhibition of human Tankyrase-1 (TNKS1) by ZT-5483 exhibited anti-parasitic activity in Toxoplasma gondii: An in silico-based, high-throughput virtual screen and in vitro approach.
Alraey Y
Mol Biochem Parasitol · 2025 Dec · PMID 41109662 · Publisher ↗
BACKGROUND AND AIM: Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the Toxoplasma gondii parasite. Given the serious side eff...
BACKGROUND AND AIM: Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the Toxoplasma gondii parasite. Given the serious side effects and recurrence of resistance, there is an unmet need to develop effective novel drugs with low toxicity against T. gondii. This study aims to identify novel anti-parasitic compounds targeting human Tankyrase-1 involved in T. gondii infection using bioinformatics and in vitro approaches. METHODS: For lead identification, high-throughput virtual screening (HTVS) against the ChemBridge library was followed by Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques. Human TNKS1 (PARP5A) colorimetric assay was performed. The RH-2F strain of T. gondii tachyzoites that expressed beta-galactosidase was maintained in the human foreskin fibroblasts (HFFs) to determine the parasite growth-inhibitory efficacy of the lead candidate. MTT assay was used to detect the inhibition rate on host cell viability. RESULTS: HTVS identified ZT-5483 with favorable binding affinities of 8.8 kcal/mol towards TNKS1. Molecular dynamic simulations demonstrated stable binding interactions for ZT-5483 and TNKS1 with Root Mean Square Deviation values around 0.04 nm. The ΔG binding calculation was -43.09 kcal/mol, favoring sturdy binding. ADME analysis supported favorable small-molecule characteristics. ZT-5483 dose responsively inhibited TNKS1 activity with an IC value of 140.8 nM. ZT-5483 suppressed the parasite growth with an IC value of 297.8 nM. The compound's cytotoxicity to HFF host cells (TD value) was determined to be 3354 nM. The in vitro toxicity index (TI) of ZT-5483 was 11.26 based on the IC and TD values. CONCLUSION: Together, these findings suggest that ZT-5483 could be a potential novel candidate against T. gondii. However, further preclinical and pharmacological evaluations are warranted.
Stage-dependent expression and vacuolar localization of Plasmodium berghei chloroquine resistance transporter (CRT).
Korbmacher F, Rauch M, Kenthirapalan S … +3 more , Kooij TWA, Maier AG, Matuschewski K
Mol Biochem Parasitol · 2025 Dec · PMID 41077253 · Publisher ↗
Plasmodium parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we...
Plasmodium parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we profiled the spatio-temporal expression of CRT during life cycle progression employing CRT-mCherry Plasmodium berghei parasites. We show that CRT is expressed during asexual blood stage growth and localizes to the hemozoin-containing digestive vacuole. The compartmentalized CRT-mCherry signal is also abundant in gametocytes and ookinetes, indicating that CRT continues to exert important functions in this digestive organelle up until mosquito midgut colonization. Expression is switched off during sporogony and early liver infection but CRT-mCherry is present again in mature liver stages, likely in preparation for blood infection. Together, visualization of the P. berghei digestive vacuole by endogenous tagging of PbCRT revealed expression of this transport protein and the presence of this cellular compartment beyond asexual propagation inside erythrocytes.
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