Ana Paula Lula Costa , Jordi Bascompte , Andre Andrian Padial
{"title":"Modularity in host-parasite mixed networks: interaction configuration shifts based on human perturbation and parasitism form","authors":"Ana Paula Lula Costa , Jordi Bascompte , Andre Andrian Padial","doi":"10.1016/j.ijpara.2023.04.004","DOIUrl":"10.1016/j.ijpara.2023.04.004","url":null,"abstract":"<div><p>Parasitism is an association based on host individual traits and environmental factors. The complexity of this type of interaction is often lost when studying species-by-species interaction networks. Here we analyze changes in modularity - a metric describing groups of nodes interacting much more frequently among themselves than they do with nodes of other modules, considering the host individual variation and the different forms of parasitism: ecto- and endo-parasitism. For this, we studied mixed networks: bipartite networks comprising host individuals and parasite species as two sets of nodes interacting with each other. We used a fish-parasite mixed network from a highly perturbed coastal river to understand how an anthropogenic perturbation gradient influences the modular structure of host-parasite networks. In addition, we tested how host individual traits drove module configuration within host-parasite mixed networks. Our results showed that different forms of parasitism respond differently to the environment: modularity in fish-ectoparasite networks increased with human perturbation, but modularity was not related to human perturbation in fish-endoparasite networks. In addition, mixed network modules were intrinsically related to individual variation, with host intensity of infection being the most important trait, regardless of the parasite’s life form. The effect of total abundance over network structure indicates signs of changes in community equilibrium, with an increase in species with opportunistic behaviors. Module composition was also related to host fitness and body size, which were most predictive in more preserved and diverse river sections. Overall, our results indicate that host-parasite networks are sensitive to ecological gradients marked by human perturbation and that host individual fitness helps to determine network structure.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javier Gandasegui , Rosemonde I. Power , Emily Curry , Daisy Ching-Wai Lau , Connor M. O'Neill , Adrian Wolstenholme , Roger Prichard , Jan Šlapeta , Stephen R. Doyle
{"title":"Genome structure and population genomics of the canine heartworm Dirofilaria immitis","authors":"Javier Gandasegui , Rosemonde I. Power , Emily Curry , Daisy Ching-Wai Lau , Connor M. O'Neill , Adrian Wolstenholme , Roger Prichard , Jan Šlapeta , Stephen R. Doyle","doi":"10.1016/j.ijpara.2023.07.006","DOIUrl":"10.1016/j.ijpara.2023.07.006","url":null,"abstract":"<div><p>The heartworm, <em>Dirofilaria immitis,</em> is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of <em>D. immitis</em> to enable a more precise understanding of how genetic variation is distributed within and between parasite populations worldwide, which will inform the likelihood and rate by which parasites, and in turn, resistant alleles, might spread. We have guided the scaffolding of a recently published genome assembly for <em>D. immitis</em> (ICBAS_JMDir_1.0) using the chromosomal-scale reference genomes of <em>Brugia malayi</em> and <em>Onchocerca volvulus,</em> resulting in an 89.5 Mb assembly composed of four autosomal- and one sex-linked chromosomal-scale scaffolds representing 99.7% of the genome. Publicly available and new whole-genome sequencing data from 32 <em>D. immitis</em> samples from Australia, Italy and the USA were assessed using principal component analysis, nucleotide diversity (Pi) and absolute genetic divergence (Dxy) to characterise the global genetic structure and measure within- and between-population diversity. These population genetic analyses revealed broad-scale genetic structure among globally diverse samples and differences in genetic diversity between populations; however, fine-scale subpopulation analysis was limited and biased by differences between sample types. Finally, we mapped single nucleotide polymorphisms previously associated with macrocyclic lactone resistance in the new genome assembly, revealing the physical linkage of high-priority variants on chromosome 3, and determined their frequency in the studied populations. This new chromosomal assembly for <em>D. immitis</em> now allows for a more precise investigation of selection on genome-wide genetic variation and will enhance our understanding of parasite transmission and the spread of genetic variants responsible for resistance to treatment.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0020751923001844/pdfft?md5=a0929a4435f68b3052110cfec5d121f0&pid=1-s2.0-S0020751923001844-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bovine sarcocystosis: Sarcocystis species, diagnosis, prevalence, economic and public health considerations, and association of Sarcocystis species with eosinophilic myositis in cattle","authors":"J.P. Dubey, B.M. Rosenthal","doi":"10.1016/j.ijpara.2022.09.009","DOIUrl":"10.1016/j.ijpara.2022.09.009","url":null,"abstract":"<div><p>Infections by <em>Sarcocystis</em> in cattle are ubiquitous worldwide. There is considerable debate concerning the identity of <em>Sarcocystis</em> spp. in cattle. Proper diagnosis of <em>Sarcocystis</em> spp. is important to assess their economic and public health importance. Currently there are seven named species: <em>Sarcocystis hirsuta, Sarcocystis cruzi, Sarcocystis hominis, Sarcocystis bovifelis, arcocystis heydorni, Sarcocystis bovini</em> and <em>Sarcocystis rommeli</em>. Additionally, there are unnamed <em>Sarcocystis</em> spp. Two species, <em>S. hominis</em> and <em>S. heydorni,</em> are zoonotic. One out of seven species (<em>S. hirsuta,</em> contracted from cats) forms macroscopic cysts which can be visible during carcass inspection. Current molecular characterization is based on DNA extracted from sarcocysts from naturally infected cattle because DNA was not characterized from tissues of experimentally infected cattle or feces of experimentally infected definitive hosts. <em>Sarcocystis cruzi</em> (transmitted via canids) is recognized as the most pathogenic species and it causes abortion, low milk yield, poor body growth, and outbreaks of clinical sarcocystosis and death. Additionally, <em>Sarcocystis</em> infections have been linked to an inflammatory condition of striated muscles termed bovine eosinophilic myositis (BEM). Cattle affected by BEM appear clinically normal. Diagnosis of BEM at slaughter occurs when inspecting the carcass surface, or once the carcass has been divided into prime cuts or quarters. Sex and breed have no apparent influence on prevalence of BEM. The condition evidently occurs with equal frequency in steers, cows, and heifers. Virtually all striated muscles can be affected including skeletal muscles, the muscles of the eye, larynx, and the heart. In the USA, regulations require condemnation of BEM-affected parts, or (in severe cases) the entire carcass. These aesthetic considerations result in economic losses. Cattle experimentally infected with <em>Sarcocystis</em> did not have BEM at slaughter. Here, we review the status of <em>Sarcocystis</em> spp. and BEM in cattle including prevalence, lesions, epidemiology, and association of BEM with different species of <em>Sarcocystis</em>.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johanna Kauter , Filip Damek , Gereon Schares , Radu Blaga , Franziska Schott , Peter Deplazes , Xaver Sidler , Walter Basso
{"title":"Detection of Toxoplasma gondii-specific antibodies in pigs using an oral fluid-based commercial ELISA: Advantages and limitations","authors":"Johanna Kauter , Filip Damek , Gereon Schares , Radu Blaga , Franziska Schott , Peter Deplazes , Xaver Sidler , Walter Basso","doi":"10.1016/j.ijpara.2022.11.003","DOIUrl":"10.1016/j.ijpara.2022.11.003","url":null,"abstract":"<div><p><em>Toxoplasma gondii</em> is a major food-borne parasite and undercooked meat of infected pigs represents an important source of infection for humans. Since infections in pigs are mostly subclinical, adequate diagnostic tests for use at the farm level are pursued. Oral fluid (OF) was shown to be a promising matrix for direct and indirect detection of infections with various pathogens in pigs. The objective of this study was to assess whether <em>T. gondii</em> infections in pigs could be diagnosed using an indirect ELISA kit adapted for OF samples (OF-ELISA). Routine serology and OF-immunoblot (IB) were used as standards for the comparison. For this, serial OF samples from sows (<em>n</em> = 8) and fatteners (<em>n</em> = 3) experimentally inoculated with <em>T. gondii</em> oocysts, individual field samples from potentially exposed sows (<em>n</em> = 9) and pooled OF samples from potentially exposed group-housed fatteners (<em>n</em> = 195 pig groups, including 2,248 animals) were analysed for antibodies against <em>T. gondii</em> by ELISA. For individual animals, OF-ELISA exhibited a relative diagnostic specificity of 97.3% and a relative diagnostic sensitivity of 78.8%. In experimentally infected animals, positive OF-ELISA results were observed from 1.5 weeks post inoculation (pi) until the end of the experimental setup (8 to 30 weeks pi); however, values below the estimated cut-off were occasionally observed in some animals despite constant seropositivity. In potentially exposed individual animals, OF- and serum-ELISA results showed 100% agreement. In group-housed fatteners, antibodies against <em>T. gondii</em> could be reliably detected by OF-ELISA in groups in which at least 25% of the animals were seropositive. This OF-ELISA, based on a commercially available serum-ELISA, may represent an interesting non-invasive screening tool for detecting pig groups with a high exposure to <em>T. gondii</em> at the farm level. The OF-ELISA may need further adjustments to consistently detect individual infected pigs, probably due to variations in OF antibody concentration over time.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10020098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alicia Colos-Arango , Andrea Largo-de la Torre , Rafael Calero-Bernal , Luis-Miguel Ortega-Mora , Javier Regidor-Cerrillo
{"title":"Short-term culture adaptation of Toxoplasma gondii archetypal II and III field isolates affects cystogenic capabilities and modifies virulence in mice","authors":"Alicia Colos-Arango , Andrea Largo-de la Torre , Rafael Calero-Bernal , Luis-Miguel Ortega-Mora , Javier Regidor-Cerrillo","doi":"10.1016/j.ijpara.2023.03.004","DOIUrl":"10.1016/j.ijpara.2023.03.004","url":null,"abstract":"<div><p>Most <em>Toxoplasma gondii</em> research has been carried out using strains maintained in the laboratory for long periods of time. Long-term passage in mice or cell culture influences <em>T. gondii</em> phenotypic traits such as the capability to produce oocysts in cats and virulence in mice. In this work, we investigated the effect of cell culture adaptation in the short term for recently obtained type II (<em>Tg</em>ShSp1 (Genotype ToxoDB#3), <em>Tg</em>ShSp2 (#1), <em>Tg</em>ShSp3 (#3) and <em>Tg</em>ShSp16 (#3)) and type III (#2) isolates (<em>Tg</em>ShSp24 and <em>Tg</em>PigSp1). With this purpose, spontaneous and alkaline stress-induced cyst formation in Vero cells during 40 passages, from passage 10 (<em>p</em>10) to 50 (<em>p</em>50), and isolate virulence at <em>p</em>10 versus <em>p</em>50 were studied using a harmonized bioassay method in Swiss/CD1 mice. <em>T. gondii</em> cell culture maintenance showed a drastic loss of spontaneous and induced production of mature cysts after ≈25–30 passages. The <em>Tg</em>ShSp1, <em>Tg</em>ShSp16 and <em>Tg</em>ShSp24 isolates failed to generate spontaneously formed mature cysts at <em>p</em>50. Limited cyst formation was associated with an increase in parasite growth and a shorter lytic cycle. In vitro maintenance also modified <em>T. gondii</em> virulence in mice at <em>p</em>50 with events of exacerbation, increasing cumulative morbidity for <em>Tg</em>ShSp2 and <em>Tg</em>ShSp3 isolates and mortality for <em>Tg</em>ShSp24 and <em>Tg</em>PigSp1 isolates, or attenuation, with absence of mortality and severe clinical signs for <em>Tg</em>ShSp16, and better control of the infection with the lowest parasite and cyst burdens in lungs and brain for the <em>Tg</em>ShSp1 isolate. The present findings show deep changes in relevant phenotypic traits in laboratory-adapted <em>T. gondii</em> isolates and open new discussion about their use for inferring keys to parasite biology and virulence.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9649119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Sophia Feix, Teresa Cruz-Bustos, Bärbel Ruttkowski, Anja Joachim
{"title":"In vitro cultivation methods for coccidian parasite research","authors":"Anna Sophia Feix, Teresa Cruz-Bustos, Bärbel Ruttkowski, Anja Joachim","doi":"10.1016/j.ijpara.2022.10.002","DOIUrl":"10.1016/j.ijpara.2022.10.002","url":null,"abstract":"<div><p>The subclass Coccidia comprises a large group of protozoan parasites, including important pathogens of humans and animals such as <em>Toxoplasma gondii, Neospora caninum, Eimeria</em> spp<em>.,</em> and <em>Cystoisospora</em> spp. Their life cycle includes a switch from asexual to sexual stages and is often restricted to a single host species. Current research on coccidian parasites focuses on cell biology and the underlying mechanisms of protein expression and trafficking in different life stages, host cell invasion and host-parasite interactions. Furthermore, novel anticoccidial drug targets are evaluated. Given the variety of research questions and the requirement to reduce and replace animal experimentation, in vitro cultivation of Coccidia needs to be further developed and refined to meet these requirements. For these purposes, established culture systems are constantly improved. In addition, new in vitro culture systems lately gained considerable importance in research on Coccidia. Well established and optimized in vitro cultures of monolayer cells can support the viability and development of parasite stages and even allow completion of the life cycle in vitro, as shown for <em>Cystoisospora suis</em> and <em>Eimeria tenella.</em> Furthermore, new three-dimensional cell culture models are used for propagation of <em>Cryptosporidium</em> spp. (close relatives of the coccidians), and the infection of three-dimensional organoids with <em>T. gondii</em> also gained popularity as the interaction between the parasite and host tissue can be studied in more detail. The latest advances in three-dimensional culture systems are organ-on-a-chip models, that to date have only been tested for <em>T. gondii</em> but promise to accelerate research in other coccidians. Lastly, the completion of the life cycle of <em>C. suis</em> and <em>Cryptosporidium parvum</em> was reported to continue in a host cell-free environment following the first occurrence of asexual stages. Such axenic cultures are becoming increasingly available and open new avenues for research on parasite life cycle stages and novel intervention strategies.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Fernández-Álvarez, Pilar Horcajo, Alejandro Jiménez-Meléndez, Carlos Diezma-Díaz, Ignacio Ferre, Iván Pastor-Fernández, Luis Miguel Ortega-Mora, Gema Álvarez-García
{"title":"Transcriptional changes associated with apoptosis and type I IFN underlie the early interaction between Besnoitia besnoiti tachyzoites and monocyte-derived macrophages","authors":"María Fernández-Álvarez, Pilar Horcajo, Alejandro Jiménez-Meléndez, Carlos Diezma-Díaz, Ignacio Ferre, Iván Pastor-Fernández, Luis Miguel Ortega-Mora, Gema Álvarez-García","doi":"10.1016/j.ijpara.2023.05.002","DOIUrl":"10.1016/j.ijpara.2023.05.002","url":null,"abstract":"<div><p><em>Besnoitia besnoiti</em>-infected bulls may develop severe systemic clinical signs and orchitis that may ultimately cause sterility during the acute infection. Macrophages might play a relevant role in pathogenesis of the disease and the immune response raised against <em>B. besnoiti</em> infection. This study aimed to dissect the early interaction between <em>B. besnoiti</em> tachyzoites and primary bovine monocyte-derived macrophages in vitro. First, the <em>B. besnoiti</em> tachyzoite lytic cycle was characterized. Next, dual transcriptomic profiling of <em>B. besnoiti</em> tachyzoites and macrophages was conducted at early infection (4 and 8 h p.i.) by high-throughput RNA sequencing. Macrophages inoculated with heat-killed tachyzoites (MO-hkBb) and non-infected macrophages (MO) were used as controls. <em>Besnoitia besnoiti</em> was able to invade and proliferate in macrophages. Upon infection, macrophage activation was demonstrated by morphological and transcriptomic changes. Infected macrophages were smaller, round and lacked filopodial structures, which might be associated with a migratory phenotype demonstrated in other apicomplexan parasites. The number of differentially expressed genes (DEGs) increased substantially during infection. In <em>B. besnoiti</em>-infected macrophages (MO-Bb), apoptosis and mitogen-activated protein kinase (MAPK) pathways were regulated at 4 h p.i., and apoptosis was confirmed by TUNEL assay. The <em>Herpes simplex</em> virus 1 infection pathway was the only significantly enriched pathway in MO-Bb at 8 h p.i. Relevant DEGs of the <em>Herpes simplex</em> virus 1 infection (<em>IFNα</em>) and the apoptosis pathways (<em>CHOP-2</em>) were also significantly regulated in the testicular parenchyma of naturally infected bulls. Furthermore, the parasite transcriptomic analysis revealed DEGs mainly related to host cell invasion and metabolism. These results provide a deep overview of the earliest macrophage modulation by <em>B. besnoiti</em> that may favour parasite survival and proliferation in a specialized phagocytic immune cell. Putative parasite effectors were also identified.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9651795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew Hemphill, Alexandre Leitão, Luis-Miguel Ortega-Mora, Brian M. Cooke
{"title":"ApicoWplexa 2022: 6th international meeting on apicomplexan parasites in farm animals","authors":"Andrew Hemphill, Alexandre Leitão, Luis-Miguel Ortega-Mora, Brian M. Cooke","doi":"10.1016/j.ijpara.2023.05.003","DOIUrl":"10.1016/j.ijpara.2023.05.003","url":null,"abstract":"","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The turkey ascarid, Ascaridia dissimilis, as a model genetic system","authors":"J.B. Collins, Erik C. Andersen","doi":"10.1016/j.ijpara.2022.10.005","DOIUrl":"10.1016/j.ijpara.2022.10.005","url":null,"abstract":"<div><p>Parasitic nematodes cause significant effects on humans each year, with the most prevalent being <em>Ascaris lumbricoides</em>. Benzimidazoles (BZ) are the most widely used anthelmintic drug in humans, and although the biology of resistance to this drug class is understood in some species, resistance is poorly characterized in ascarids. Models such as <em>Caenorhabditis elegans</em> were essential in developing our current understanding of BZ resistance, but more closely related model nematodes are needed to understand resistance in ascarids. Here, we propose a new ascarid model species that infects turkeys, <em>Ascaridia dissimilis</em>, to develop a better understanding of BZ resistance.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evgeny G. Chulkov , Oleg Palygin , Nawal A. Yahya , Sang-Kyu Park , Jonathan S. Marchant
{"title":"Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel","authors":"Evgeny G. Chulkov , Oleg Palygin , Nawal A. Yahya , Sang-Kyu Park , Jonathan S. Marchant","doi":"10.1016/j.ijpara.2022.11.005","DOIUrl":"10.1016/j.ijpara.2022.11.005","url":null,"abstract":"<div><p>Ion channels have proved to be productive targets for anthelmintic chemotherapy. One example is the recent discovery of a parasitic flatworm ion channel targeted by praziquantel (PZQ), the main clinical therapy used for treatment of schistosomiasis. The ion channel activated by PZQ – a transient receptor potential ion channel of the melastatin subfamily, named TRPM<sub>PZQ</sub> – is a Ca<sup>2+</sup>-permeable ion channel expressed in all parasitic flatworms that are PZQ-sensitive. However, little is currently known about the electrophysiological properties of this target that mediates the deleterious action of PZQ on many trematodes and cestodes. Here, we provide a detailed biophysical characterization of the properties of <em>Schistosoma mansoni</em> TRPM<sub>PZQ</sub> channel (<em>Sm</em>.TRPM<sub>PZQ</sub>) in response to PZQ. Single channel electrophysiological analysis demonstrated that <em>Sm</em>.TRPM<sub>PZQ</sub> when activated by PZQ is a non-selective, large conductance, voltage-insensitive cation channel that displays distinct properties from human TRPM paralogs. <em>Sm</em>.TRPM<sub>PZQ</sub> is Ca<sup>2+</sup>-permeable but does not require Ca<sup>2+</sup> for channel gating in response to PZQ. TRPM<sub>PZQ</sub> from <em>Schistosoma japonicum</em> (<em>Sj</em>.TRPM<sub>PZQ</sub>) and <em>Schistosoma haematobium</em> (<em>Sh</em>.TRPM<sub>PZQ</sub>) displayed similar characteristics. Profiling <em>Sm</em>.TRPM<sub>PZQ</sub> responsiveness to PZQ has established a biophysical signature for this channel that will aid future investigation of endogenous TRPM<sub>PZQ</sub> activity, as well as analyses of endogenous and exogenous regulators of this novel, druggable antiparasitic target.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}