International Journal of Molecular Sciences

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21 pages, 4074 KiB

Open AccessArticle

A Structural In Silico Analysis of Novel Epitopes from Toxoplasma gondii Proteins for the Serodiagnosis of Toxoplasmosis

by Angelis del Valle Benitez Betancourt, Tamires Lopes Silva, Débora Karolla de Freitas Oliveira, Nilson Nicolau-Junior, João Luis Garcia, Ricardo Toshio Fujiwara, Tiago Wilson Patriarca Mineo and José Roberto Mineo

Int. J. Mol. Sci. 2025, 26(10), 4689; https://doi.org/10.3390/ijms26104689 - 14 May 2025

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Abstract

Toxoplasmosis is a widely spread zoonosis worldwide, considered one of the most important parasitic infections that affect global public health, and usually, it is not correctly diagnosed. Serological tests for the diagnosis of Toxoplasma gondii infection have limitations in differentiating acute from chronic [...] Read more.

Toxoplasmosis is a widely spread zoonosis worldwide, considered one of the most important parasitic infections that affect global public health, and usually, it is not correctly diagnosed. Serological tests for the diagnosis of Toxoplasma gondii infection have limitations in differentiating acute from chronic infection, which is important to determine the appropriate clinical management and treatment, mainly in pregnant women and immunocompromised individuals infected by this parasite. The present study aimed to characterize immunogenic epitopes from T. gondii immunodominant antigens, as SAG1(SRS29B), SAG2A (SRS34A), GRA1, GRA2, GRA3, GRA5, GRA6, GRA7, MAG1, BSR4, and CCp5A, by investigating if these parasite components might emerge as alternatives to improve the diagnosis of toxoplasmosis. A detailed comparative in silico analysis was used for this purpose. Once the protein sequences were retrieved from the ToxoDB database, different parameters were calculated, including physicochemical characteristics, accessibility values, and antigenicity. Multiple sequence alignment, 3D structures modeling, and the validation of 3D structures were also performed among all 11 peptides. Considering the results from the combination of all parameters analyzed, it can be hypothesized that the linear epitopes from SAG1, GRA3, and BSR4 proteins were found to be stable and hydrophilic, with a significant antigenicity score, and accessibility on the protein surface. Also, these three selected peptides were able to detect anti-T. gondii antibodies in serum samples from pigs infected by tachyzoites, when compared with control serum samples, obtained from the same naïve animals and tested by ELISA, demonstrating remarkable difference in terms of reactivity. Taken together, as our study addresses a critical challenge in the serodiagnosis of toxoplasmosis, particularly in gestational and congenital infections, where false-positive and false-negative results often arise from the use of native or recombinant antigens of T. gondii, our findings highlight the potential of synthetic peptides derived from novel epitopes of this parasite as alternative tools for the development of more accurate immunodiagnostic assays for toxoplasmosis. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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17 pages, 9016 KiB

Open AccessArticle

Interaction of Serratia proteamaculans with Integrins Activates Invasion-Promoting Signaling Pathways

by Olga Tsaplina

Int. J. Mol. Sci. 2025, 26(9), 3955; https://doi.org/10.3390/ijms26093955 - 22 Apr 2025

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Abstract

The opportunistic bacteria Serratia proteamaculans are able to penetrate human cells. It was previously shown that the bacterial surface protein OmpX promotes bacterial adhesion. In addition, infection with bacteria that synthesize the OmpX protein enhances the expression of EGFR and β1 integrin involved [...] Read more.

The opportunistic bacteria Serratia proteamaculans are able to penetrate human cells. It was previously shown that the bacterial surface protein OmpX promotes bacterial adhesion. In addition, infection with bacteria that synthesize the OmpX protein enhances the expression of EGFR and β1 integrin involved in the invasion of S. proteamaculans. Therefore, this work was aimed at determining the mechanism of interaction of S. proteamaculans with receptors of eukaryotic cells. Both integrin-linked kinase (ILK) and EGFR tyrosine kinase have been shown to be involved in the invasion of these bacteria. During infection, EGFR is first phosphorylated at Tyr845, which is carried out by c-Src kinase transmitting a signal from nearby receptors. The S. proteamaculans invasion depends on c-Src and focal adhesion kinase (FAK), which can both transmit a signal between β1 integrin and EGFR and participate in cytoskeletal rearrangements. These bacteria have been shown to interact with integrin not through the RGD binding site, and integrin binding to the RGD peptide enhances adhesion, invasion, and expression of α5 and β1 integrin subunits in response to infection. On the other hand, bacterial adhesion and increased expression of integrins during infection are caused by OmpX. Thus, OmpX interacts with integrins, and the participation of the α5 and β1 integrin subunits in the S. proteamaculans invasion allows us to assume that the receptor of OmpX is α5β1 integrin. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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19 pages, 19421 KiB

Open AccessArticle

Bioinformatics Analysis of the Glutamate-Gated Chloride Channel Family in Bursaphelenchus xylophilus

by Haixiang Li, Rui Wang, Jialiang Pan, Jie Chen and Xin Hao

Int. J. Mol. Sci. 2025, 26(8), 3477; https://doi.org/10.3390/ijms26083477 - 8 Apr 2025

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Abstract

Glutamate-gated chloride channels (GluCls), a class of ion channels found in the nerve and muscle cells of invertebrates, are involved in vital life processes. Bursaphelenchus xylophilus, the pathogen of pine wilt disease, has induced major economic and ecological losses in invaded areas [...] Read more.

Glutamate-gated chloride channels (GluCls), a class of ion channels found in the nerve and muscle cells of invertebrates, are involved in vital life processes. Bursaphelenchus xylophilus, the pathogen of pine wilt disease, has induced major economic and ecological losses in invaded areas of Asia and Europe. We identified 33 GluCls family members by sequence alignment analysis. A subsequent bioinformatic analysis revealed the physicochemical properties, protein structure, and gene expression patterns in different developmental stages. The results showed that GluCls genes are distributed across all six chromosomes of B. xylophilus. These proteins indicated a relatively conserved structure by NCBI-conserved domains and InterPro analysis. A gene structure analysis revealed that GluCls genes consist of 5 to 14 exons. Expression pattern analysis revealed BxGluCls were extensively involved in the development of second instar larvae of B. xylophilus. Furthermore, BxGluCls15, BxGluCls25, and BxGluCls28 were mainly associated with the development of eggs of B. xylophilus. BxGluCls12, BxGluCls18, and BxGluCls32 were predominantly linked to nematode resistance and adaptation. Investigation the structure and expression patterns of BxGluCls is crucial to understand the developmental trends of B. xylophilus. It also helps identify molecular targets for the development of biopesticides or drugs designed to control this nematode. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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22 pages, 4185 KiB

Open AccessArticle

Prediction and Prioritisation of Novel Anthelmintic Candidates from Public Databases Using Deep Learning and Available Bioactivity Data Sets

by Aya C. Taki, Louis Kapp, Ross S. Hall, Joseph J. Byrne, Brad E. Sleebs, Bill C. H. Chang, Robin B. Gasser and Andreas Hofmann

Int. J. Mol. Sci. 2025, 26(7), 3134; https://doi.org/10.3390/ijms26073134 - 28 Mar 2025

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Abstract

The control of socioeconomically important parasitic roundworms (nematodes) of animals has become challenging or ineffective due to problems associated with widespread resistance in these worms to most classes of chemotherapeutic drugs (anthelmintics) currently available. Thus, there is an urgent need to discover and [...] Read more.

The control of socioeconomically important parasitic roundworms (nematodes) of animals has become challenging or ineffective due to problems associated with widespread resistance in these worms to most classes of chemotherapeutic drugs (anthelmintics) currently available. Thus, there is an urgent need to discover and develop novel compounds with unique mechanisms of action to underpin effective parasite control programmes. Here, we evaluated an in silico (computational) approach to accelerate the discovery of new anthelmintics against the parasitic nematode Haemonchus contortus (barber’s pole worm) as a model system. Using a supervised machine learning workflow, we trained and assessed a multi-layer perceptron classifier on a labelled dataset of 15,000 small-molecule compounds, for which extensive bioactivity data were previously obtained for H. contortus via high-throughput screening, as well as evidence-based datasets from the peer-reviewed literature. This model achieved 83% precision and 81% recall on the class of ‘active’ compounds during testing, despite a high imbalance in the training data, with only 1% of compounds carrying this label. The trained model was then used to infer nematocidal candidates by in silico screening of 14.2 million compounds from the ZINC15 database. An experimental assessment of 10 of these candidates showed significant inhibitory effects on the motility and development of H. contortus larvae and adults in vitro, with two compounds exhibiting high potency for further exploration as lead candidates. These findings indicate that the present machine learning-based approach could accelerate the in silico prediction and prioritisation of anthelmintic small molecules for subsequent in vitro and in vivo validations. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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24 pages, 13501 KiB

Open AccessArticle

Host–Parasite Interactions in Toxoplasma gondii-Infected Cells: Roles of Mitochondria, Microtubules, and the Parasitophorous Vacuole

by Sailen Barik and Joel Andrews

Int. J. Mol. Sci. 2024, 25(24), 13459; https://doi.org/10.3390/ijms252413459 - 16 Dec 2024

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Abstract

An intracellular protozoan, the Apicomplexan parasite Toxoplasma gondii (T. gondii) infects nucleated cells, in which it triggers the formation of a specialized membrane-confined cytoplasmic vacuole, named the parasitophorous vacuole (PV). One of the most prominent events in the parasite’s intracellular life [...] Read more.

An intracellular protozoan, the Apicomplexan parasite Toxoplasma gondii (T. gondii) infects nucleated cells, in which it triggers the formation of a specialized membrane-confined cytoplasmic vacuole, named the parasitophorous vacuole (PV). One of the most prominent events in the parasite’s intracellular life is the congregation of the host cell mitochondria around the PV. However, the significance of this event has remained largely unsolved since the parasite itself possesses a functional mitochondrion, which is essential for its replication. Here, we explore several fundamental aspects of the interaction between the PV and the host cell mitochondria. They include the detailed features of the congregation, the nature and mechanism of the mitochondrial travel to the PV, and the potential significance of the migration and congregation. Using a combination of biochemical assays, high-resolution imaging, and RNAi-mediated knockdown, we show that: (i) mitochondrial travel to the PV starts very early in parasite infection, as soon as the smallest PV takes shape; (ii) the travel utilizes the contractile microtubular network of the host cell; and (iii) near the end of the parasitic life cycle, when most PVs have reached their largest sustainable size and are about to lyse in order to release the progeny parasites, the associated mitochondria change their usual elongated shape to small spheres, apparently resulting from increased fission. Intriguingly, despite the well-known mitochondrial role as a major producer of cellular ATP, the parasite does not seem to use cellular mitochondrial ATP. Together, these findings may serve as foundations for future research in host–parasite interaction, particularly in the elucidation of its mechanisms, and the possible development of novel antiparasitic drug regimens. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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18 pages, 87123 KiB

Open AccessArticle

Molecular Characteristics of the Malate Dehydrogenase (MDH) Gene Family in Spirometra mansoni (Cestoda: Diphyllobothriidea)

by Ruijie Wang, Jie Hao, Chengyue Cao, Jing Li and Xi Zhang

Int. J. Mol. Sci. 2024, 25(16), 8802; https://doi.org/10.3390/ijms25168802 - 13 Aug 2024

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Abstract

The plerocercoid larva of Spirometra mansoni can cause a parasitic zoonosis—sparganosis. Malate dehydrogenase (MDH) plays a very important role in the life activities of parasites. However, little is known about the MDH family in S. mansoni. We identified eight new MDH members [...] Read more.

The plerocercoid larva of Spirometra mansoni can cause a parasitic zoonosis—sparganosis. Malate dehydrogenase (MDH) plays a very important role in the life activities of parasites. However, little is known about the MDH family in S. mansoni. We identified eight new MDH members in S. mansoni in this study. Clustering analysis divided SmMDHs into two groups and revealed patterns similar to the conserved motif organization. RT–qPCR suggested that five MDHs were highly expressed in the mature proglottid and that three MDHs were highly expressed in the gravid proglottid. Phylogenetic analysis revealed that SmMDHs contain both conserved family members and members in the process of further diversification. rSmMDH has an NAD binding domain, a dimer interface and a substrate binding domain. Natural SmMDH was immunolocalized in the tissues and follicles around the uterus in the mature or gravid proglottid and eggshells. The maximum forward and reverse reaction activities of rSmMDH were observed at pH 8.5 and 9.0, respectively. The optimum temperature for enzyme activity was 37 °C in the forward reaction and 40 °C in the reverse reaction. These results lay the foundation for studying the molecular functions and mechanisms of MDHs in S. mansoni and related taxa. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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10 pages, 1115 KiB

Open AccessArticle

The Mitogenome of the Haecon-5 Strain of Haemonchus contortus and a Comparative Analysis of Its Nucleotide Variation with Other Laboratory Strains

by Yuanting Zheng, Neil D. Young, Jiangning Song and Robin B. Gasser

Int. J. Mol. Sci. 2024, 25(16), 8765; https://doi.org/10.3390/ijms25168765 - 12 Aug 2024

Cited by 1 | Viewed by 1426

Abstract

Haemonchus contortus (the barber’s pole worm)—a highly pathogenic gastric nematode of ruminants—causes significant economic losses in the livestock industry worldwide. H. contortus has become a valuable model organism for both fundamental and applied research (e.g., drug and vaccine discovery) because of the availability [...] Read more.

Haemonchus contortus (the barber’s pole worm)—a highly pathogenic gastric nematode of ruminants—causes significant economic losses in the livestock industry worldwide. H. contortus has become a valuable model organism for both fundamental and applied research (e.g., drug and vaccine discovery) because of the availability of well-defined laboratory strains (e.g., MHco3(ISE).N1 in the UK and Haecon-5 in Australia) and genomic, transcriptomic and proteomic data sets. Many recent investigations have relied heavily on the use of the chromosome-contiguous genome of MHco3(ISE).N1 in the absence of a genome for Haecon-5. However, there has been no genetic comparison of these and other strains to date. Here, we assembled and characterised the mitochondrial genome (14.1 kb) of Haecon-5 and compared it with that of MHco3(ISE).N1 and two other strains (i.e., McMaster and NZ_Hco_NP) from Australasia. We detected 276 synonymous and 25 non-synonymous single nucleotide polymorphisms (SNPs) within Haecon-5. Between the Haecon-5 and MHco3(ISE).N1 strains, we recorded 345 SNPs, 31 of which were non-synonymous and linked to fixed amino acid differences in seven protein-coding genes (nad5, nad6, nad1, atp6, nad2, cytb and nad4) between these strains. Pronounced variation (344 and 435 SNPs) was seen between Haecon-5 and each of the other two strains from Australasia. The question remains as to what impact these mitogenomic mutations might have on the biology and physiology of H. contortus, which warrants exploration. The high degree of mitogenomic variability recorded here among these strains suggests that further work should be undertaken to assess the nature and extent of the nuclear genomic variation within H. contortus. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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12 pages, 2430 KiB

Open AccessArticle

Nematode Galectin Inhibits Basophilic Leukaemia RBL-2H3 Cells Apoptosis in IgE-Mediated Activation

by Marta Maruszewska-Cheruiyot, Ludmiła Szewczak, Katarzyna Krawczak-Wójcik, Michael James Stear and Katarzyna Donskow-Łysoniewska

Int. J. Mol. Sci. 2024, 25(13), 7419; https://doi.org/10.3390/ijms25137419 - 6 Jul 2024

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Abstract

Mast cells are essential immune cells involved in the host’s defence against gastrointestinal nematodes. To evade the immune response, parasitic nematodes produce a variety of molecules. Galectin 1, produced by Teladorsagia circumcincta (Tci-gal-1), reduces mast cell degranulation and selectively regulates mediator production and [...] Read more.

Mast cells are essential immune cells involved in the host’s defence against gastrointestinal nematodes. To evade the immune response, parasitic nematodes produce a variety of molecules. Galectin 1, produced by Teladorsagia circumcincta (Tci-gal-1), reduces mast cell degranulation and selectively regulates mediator production and release in an IgE-dependent manner. To uncover the activity of Tci-gal-1, we have examined the effect of the protein on gene expression, protein production, and apoptosis in activated basophilic leukaemia RBL-2H3 cells. Rat RBL-2H3 cells were activated with anti-DNP IgE and DNP-HSA, and then treated with Tci-gal-1. Microarray analysis was used to examine gene expression. The levels of several apoptosis-related molecules and cytokines were determined using antibody arrays and ELISA. Early and late apoptosis was evaluated cytometrically. Degranulation of cells was determined by a β-hexosaminidase release assay. Treatment of activated RBL-2H3 cells with Tci-gal-1 resulted in inhibited apoptosis and decreased degranulation, although we did not detect significant changes in gene expression. The production of pro-apoptotic molecules, receptor for advanced glycation end products (RAGE) and Fas ligand (FasL), and the cytokines IL-9, IL-10, IL-13, TNF-α, and IL-2 was strongly inhibited. Tci-gal-1 modulates apoptosis, degranulation, and production of cytokines by activated RBL-2H3 cells without detectable influence on gene transcription. This parasite protein is crucial for modulation of the protective immune response and the inhibition of chronic inflammation driven by mast cell activity. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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14 pages, 1163 KiB

Open AccessArticle

Enhanced Genomic and Transcriptomic Resources for Trichinella pseudospiralis and T. spiralis to Underpin the Discovery of Molecular Differences between Stages and Species

by Pasi K. Korhonen, Giuseppe La Rosa, Sunita B. Sumanam, Maria Angeles Gomez Morales, Alessandra Ludovisi, Edoardo Pozio, Daniele Tonanzi, Bill C. H. Chang, Neil D. Young and Robin B. Gasser

Int. J. Mol. Sci. 2024, 25(13), 7366; https://doi.org/10.3390/ijms25137366 - 5 Jul 2024

Cited by 1 | Viewed by 1693

Abstract

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of [...] Read more.

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host–parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin—with possible roles in modulating host immune responses and facilitating parasite survival—were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella–host interactions might offer possible avenues for developing new interventions against trichinellosis. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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13 pages, 2643 KiB

Open AccessArticle

Inference of Essential Genes of the Parasite Haemonchus contortus via Machine Learning

by Túlio L. Campos, Pasi K. Korhonen, Neil D. Young, Tao Wang, Jiangning Song, Richard Marhoefer, Bill C. H. Chang, Paul M. Selzer and Robin B. Gasser

Int. J. Mol. Sci. 2024, 25(13), 7015; https://doi.org/10.3390/ijms25137015 - 27 Jun 2024

Cited by 3 | Viewed by 2254

Abstract

Over the years, comprehensive explorations of the model organisms Caenorhabditis elegans (elegant worm) and Drosophila melanogaster (vinegar fly) have contributed substantially to our understanding of complex biological processes and pathways in multicellular organisms generally. Extensive functional genomic–phenomic, genomic, transcriptomic, and proteomic data sets [...] Read more.

Over the years, comprehensive explorations of the model organisms Caenorhabditis elegans (elegant worm) and Drosophila melanogaster (vinegar fly) have contributed substantially to our understanding of complex biological processes and pathways in multicellular organisms generally. Extensive functional genomic–phenomic, genomic, transcriptomic, and proteomic data sets have enabled the discovery and characterisation of genes that are crucial for life, called ‘essential genes’. Recently, we investigated the feasibility of inferring essential genes from such data sets using advanced bioinformatics and showed that a machine learning (ML)-based workflow could be used to extract or engineer features from DNA, RNA, protein, and/or cellular data/information to underpin the reliable prediction of essential genes both within and between C. elegans and D. melanogaster. As these are two distantly related species within the Ecdysozoa, we proposed that this ML approach would be particularly well suited for species that are within the same phylum or evolutionary clade. In the present study, we cross-predicted essential genes within the phylum Nematoda (evolutionary clade V)—between C. elegans and the pathogenic parasitic nematode H. contortus—and then ranked and prioritised H. contortus proteins encoded by these genes as intervention (e.g., drug) target candidates. Using strong, validated predictors, we inferred essential genes of H. contortus that are involved predominantly in crucial biological processes/pathways including ribosome biogenesis, translation, RNA binding/processing, and signalling and which are highly transcribed in the germline, somatic gonad precursors, sex myoblasts, vulva cell precursors, various nerve cells, glia, or hypodermis. The findings indicate that this in silico workflow provides a promising avenue to identify and prioritise panels/groups of drug target candidates in parasitic nematodes for experimental validation in vitro and/or in vivo. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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21 pages, 2105 KiB

Open AccessArticle

The Development of Toxoplasma gondii Recombinant Trivalent Chimeric Proteins as an Alternative to Toxoplasma Lysate Antigen (TLA) in Enzyme-Linked Immunosorbent Assay (ELISA) for the Detection of Immunoglobulin G (IgG) in Small Ruminants

by Bartłomiej Tomasz Ferra, Maciej Chyb, Karolina Sołowińska, Lucyna Holec-Gąsior, Marta Skwarecka, Karolina Baranowicz and Justyna Gatkowska

Int. J. Mol. Sci. 2024, 25(8), 4384; https://doi.org/10.3390/ijms25084384 - 16 Apr 2024

Cited by 1 | Viewed by 2504

Abstract

This study presents an evaluation of seventeen newly produced recombinant trivalent chimeric proteins (containing the same immunodominant fragment of SAG1 and SAG2 of Toxoplasma gondii antigens, and an additional immunodominant fragment of one of the parasite antigens, such as AMA1, GRA1, GRA2, GRA5, [...] Read more.

This study presents an evaluation of seventeen newly produced recombinant trivalent chimeric proteins (containing the same immunodominant fragment of SAG1 and SAG2 of Toxoplasma gondii antigens, and an additional immunodominant fragment of one of the parasite antigens, such as AMA1, GRA1, GRA2, GRA5, GRA6, GRA7, GRA9, LDH2, MAG1, MIC1, MIC3, P35, and ROP1) as a potential alternative to the whole-cell tachyzoite lysate (TLA) used in the detection of infection in small ruminants. These recombinant proteins, obtained by genetic engineering and molecular biology methods, were tested for their reactivity with specific anti-Toxoplasma IgG antibodies contained in serum samples of small ruminants (192 samples of sheep serum and 95 samples of goat serum) using an enzyme-linked immunosorbent assay (ELISA). The reactivity of six recombinant trivalent chimeric proteins (SAG1-SAG2-GRA5, SAG1-SAG2-GRA9, SAG1-SAG2-MIC1, SAG1-SAG2-MIC3, SAG1-SAG2-P35, and SAG1-SAG2-ROP1) with IgG antibodies generated during T. gondii invasion was comparable to the sensitivity of TLA-based IgG ELISA (100%). The obtained results show a strong correlation with the results obtained for TLA. This suggests that these protein preparations may be a potential alternative to TLA used in commercial tests and could be used to develop a cheaper test for the detection of parasite infection in small ruminants. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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12 pages, 941 KiB

Open AccessReview

Advances in Anthelmintic Target Identification

by Harrison T. Shanley, Tao Wang, Aya C. Taki, Joseph J. Byrne, Bill C. H. Chang, Brad E. Sleebs and Robin B. Gasser

Int. J. Mol. Sci. 2025, 26(8), 3738; https://doi.org/10.3390/ijms26083738 - 15 Apr 2025

Viewed by 471

Abstract

Parasitic nematodes pose a significant threat to human and animal health, causing widespread morbidity and substantial socioeconomic losses globally. Despite the utility of anthelmintic drugs in parasite control, the emergence of widespread resistance necessitates the discovery of novel interventions. Advances through the use [...] Read more.

Parasitic nematodes pose a significant threat to human and animal health, causing widespread morbidity and substantial socioeconomic losses globally. Despite the utility of anthelmintic drugs in parasite control, the emergence of widespread resistance necessitates the discovery of novel interventions. Advances through the use of whole-organism phenotypic screening have identified some promising nematocidal compounds, including nemacol, tolfenpyrad, UMW-9729, and ABX464. This article summarises efforts in this discovery, with a focus on Haemonchus contortus and Caenorhabditis elegans as model nematodes, and discusses approaches used for drug target deconvolution, including proteomic, chemical and genetic/genomic techniques. Stability-based proteomic assays, such as thermal proteome profiling, have been useful for identifying protein targets for these compounds, shedding light on their mechanisms of action. However, challenges remain in extrapolating findings from C. elegans to parasitic nematodes, emphasising the need for validation studies. Understanding drug–target interactions in nematodes is critical for developing next-generation anthelmintics and for mitigating the growing resistance challenge. This review outlines recent progress in this area and discusses future directions in target validation and anthelmintic development to support parasite control programmes. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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21 pages, 2890 KiB

Open AccessReview

The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism

by Sylwia Klimczak, Kacper Packi, Alicja Rudek, Sylwia Wenclewska, Marcin Kurowski, Daniela Kurczabińska and Agnieszka Śliwińska

Int. J. Mol. Sci. 2024, 25(16), 8627; https://doi.org/10.3390/ijms25168627 - 7 Aug 2024

Cited by 5 | Viewed by 7693

Abstract

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This [...] Read more.

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders. Full article

(This article belongs to the Special Issue Parasite Biology and Host-Parasite Interactions: 2nd Edition)

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