Josef Krátký , Markéta Zajíčková , Aya C. Taki , Oliver Michel , Petra Matoušková , Ivan Vokřál , Karolína Štěrbová , Ondřej Vosála , Beate Lungerich , Thomas Kurz , Robin B. Gasser , Karel Harant , Lenka Skálová
{"title":"New derivatives of benzhydroxamic acid with nematocidal activity against Haemonchus contortus and Caenorhabditis elegans","authors":"Josef Krátký , Markéta Zajíčková , Aya C. Taki , Oliver Michel , Petra Matoušková , Ivan Vokřál , Karolína Štěrbová , Ondřej Vosála , Beate Lungerich , Thomas Kurz , Robin B. Gasser , Karel Harant , Lenka Skálová","doi":"10.1016/j.ijpddr.2025.100599","DOIUrl":"10.1016/j.ijpddr.2025.100599","url":null,"abstract":"<div><div>Parasitic nematodes cause a wide range of diseases in animals, including humans. However, the efficacy of existing anthelmintic drugs, commonly used to treat these infections, is waning due to the increasing prevalence of drug resistance in nematode populations. This growing challenge underscores the urgent need to discover and develop novel nematocidal drugs that target new molecular pathways. In the present study, 13 novel derivatives of benzhydroxamic acid (OMKs) were designed and synthesized. Their anthelmintic activity was tested in the parasitic nematode <em>Haemonchus contortus</em> (barber's pole worm) and the free-living nematode <em>Caenorhabditis elegans</em> and potential toxicity assessed in mammalian models. Compound OMK211 showed the most promising results. It decreased viability and motility of larval and adult stages of both nematode species and of both drug-sensitive and drug-resistant strains of <em>H. contortus</em> at micromolar concentrations with the highest efficacy in <em>H. contortus</em> adult males (IC<sub>50</sub> ∼ 1 μM). Moreover, OMK211 was not toxic in mammalians cells <em>in vitro</em> and in mice <em>in vivo</em>. Consequently, thermal proteome profiling analysis was used to infer the putative molecular target of OMK211 in <em>H. contortus</em>. The results revealed C2-domain containing protein A0A6F7Q0A8, encoded by gene HCON_00184,900, as an interacting partner of OMK211. Using advanced structural prediction and docking tools, this protein is considered an interesting putative molecular target of new nematocidal drugs as its orthologs are present in several nematodes but not in mammals. In conclusion, novel derivatives of benzhydroxamic acid represent a promising new class of potential anthelmintics, which deserve further testing.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100599"},"PeriodicalIF":4.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125291","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}
Jessica L. Home, Geoffrey I. McFadden, Christopher D. Goodman
{"title":"Resistance to apicoplast translational inhibitors in Plasmodium","authors":"Jessica L. Home, Geoffrey I. McFadden, Christopher D. Goodman","doi":"10.1016/j.ijpddr.2025.100597","DOIUrl":"10.1016/j.ijpddr.2025.100597","url":null,"abstract":"<div><div>The spread of drug-resistant <em>Plasmodium</em> threatens malaria control efforts. Thus, understanding the mechanisms of resistance is crucial for implementing effective treatments and prevention strategies. The prokaryote-like translational machinery encoded by the apicoplast is the apparent target of several antibiotics with antimalarial activity. Among them, doxycycline and clindamycin are widely used for malaria treatment and/or chemoprophylaxis. However, the mechanisms underlying <em>Plasmodium</em> resistance to apicoplast-targeting antibiotics, and the evolution of such resistance mechanisms, remain largely unknown. In this review, we summarise reported cases of resistance to apicoplast translational inhibitors uncovered in either laboratory or clinical settings. We highlight the potential evolutionary pathway of doxycycline resistance, explore why resistance to these antibiotics remains rare in the field, and assess whether expanding their use in malaria treatment and prevention is a viable strategy.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100597"},"PeriodicalIF":4.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070137","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}
Adrián Chávez-Cano , Scott C. Dawson , M. Guadalupe Ortega-Pierres
{"title":"gdSir2.1 and gdSir2.3 are involved in albendazole resistance in Giardia duodenalis via regulation of the oxidative stress response","authors":"Adrián Chávez-Cano , Scott C. Dawson , M. Guadalupe Ortega-Pierres","doi":"10.1016/j.ijpddr.2025.100596","DOIUrl":"10.1016/j.ijpddr.2025.100596","url":null,"abstract":"<div><div>Albendazole resistance in <em>Giardia duodenalis</em> includes a complex and multifactorial challenge that potentially involves non-reported pathways such as the participation of metabolic regulators. In this context, sirtuins, known as metabolic sensors in various cellular processes, have emerged as promising candidates for novel anti-parasitic treatments. To investigate their role in albendazole (ABZ) resistance, initially we analyzed the expression of sirtuins in three <em>Giardia</em> strains resistant to 8 μM, 1.5 μM and 250 μM of ABZ that were obtained in our laboratory. Additionally, we used a CRISPRi-based knockdownstrategy to repress several sirtuins in <em>Giardia</em> and analyzed the effect of sirtuins on ABZ resistance. Our findings demonstrated a significant upregulation of sirtuins gdSir2.1, gdSir2.2 and gdSir2.3 in the three distinct albendazole-resistant lines. Knockdown of gdSir2.1 and gdSir2.3 resulted in heightened parasite susceptibility to both albendazole and hydrogen peroxide. Further, our study suggested that sirtuins contribute to the regulation of reactive oxygen species (ROS) levels, oxidative DNA damage, and the expression of oxidative stress response (OSR) genes within the parasite. Collectively, our results demonstrated that gdSir2.1 and gdSir2.3 play a significant role in mediating albendazole resistance, primarily through regulating the oxidative stress response.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100596"},"PeriodicalIF":4.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947607","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}
Lúcia Mamede , Fanta Fall , Madeline Vast , Kristelle Hughes , Giorgia Martelli , Francesco Caligiore , Bernadette Govaerts , Paul A.M. Michels , Michel Frédérich , Joëlle Quetin-Leclercq
{"title":"Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei","authors":"Lúcia Mamede , Fanta Fall , Madeline Vast , Kristelle Hughes , Giorgia Martelli , Francesco Caligiore , Bernadette Govaerts , Paul A.M. Michels , Michel Frédérich , Joëlle Quetin-Leclercq","doi":"10.1016/j.ijpddr.2025.100595","DOIUrl":"10.1016/j.ijpddr.2025.100595","url":null,"abstract":"<div><div>Trypanosomiasis is a parasitic disease for which new treatments are needed due to the frequent occurrence of adverse side effects of current available drugs. Natural compounds found in traditionally used plants offer opportunities to discover innovative compounds that could prove pivotal to antitrypanosomal drug development. 3-O-<em>p</em>-(<em>Z/E</em>)-coumaroyltormentic acids (CTA) were isolated first from the West Africa-native tree <em>Vitellaria paradoxa</em> and have demonstrated quite selective <em>in vitro</em> and <em>in vivo</em> antitrypanosomal activity, despite the unknown mode of action. In this study, a metabolomics analysis using the data from both LC-HR-MS and <sup>1</sup>H-NMR described CTA's effects on <em>Trypanosoma brucei</em> after 3 h exposure under 5 or 10 x EC<sub>50</sub>. Our study shows CTA's activity impacted tryptophan metabolism and reveals potential targets in different branches of this metabolism. Our results demonstrate a likely presence of enzymes dedicated to tryptophan, like a tryptophan aminotransferase, tryptophan 2,3-dioxygenase and/or indoleamine 2,3-dioxygenase, and other enzymes of the kynurenine pathway, despite the absence of their description thus far in this species. These data further implicate that CTA's toxic effect on the tryptophan metabolism may be attributed to the decrease of the intracellular level of essential aspartate, resulting from inhibition of its aminotransferase. In resume, our study shines light on the likelihood of the tryptophan metabolism pathway presenting innovative targets toward the development of antitrypanosomal drugs. These require confirmation through functional and enzymatic studies.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100595"},"PeriodicalIF":4.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070138","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}
Anne-Charlotte Lenière , Amit Upadhyay , Jérôme Follet , Timothy P. O'Sullivan
{"title":"Effect of urea and squaramide IMPDH inhibitors on C. parvum: in vitro trial design impacts the assessment of drug efficacy","authors":"Anne-Charlotte Lenière , Amit Upadhyay , Jérôme Follet , Timothy P. O'Sullivan","doi":"10.1016/j.ijpddr.2025.100592","DOIUrl":"10.1016/j.ijpddr.2025.100592","url":null,"abstract":"<div><div>The protozoan parasite <em>Cryptosporidium</em> is the etiological agent of cryptosporidiosis, a ubiquitous diarrheic disease affecting humans and animals. Treatment options are limited, highlighting an urgent need for novel therapeutics. Despite decades of research and a wide diversity of strategies to tackle parasite metabolic pathways, no completely effective drug has been identified to date. Within targeted parasite enzymatic and metabolic pathways, the synthesis of nucleotide mediated by the inosine 5′-monophosphate dehydrogenase (IMPDH) enzyme is the focus of significant research efforts. Based on our prior studies of bacterial IMPDH inhibitors, we report herein the development and characterisation of novel inhibitors targeting <em>Cryptosporidium parvum</em> IMPDH (<em>Cp</em>IMPDH). Specifically, we synthesised heteroaryl-containing urea and squaramide analogues to evaluate their potential <em>in vitro</em> anti-<em>Cryptosporidium</em> activity. Initial screening identified nine active compounds with the most potent candidates achieving IC<sub>50</sub> values as low as 2.2 μM. Subsequent time-course experiments revealed that the molecules effectively inhibit parasite invasion and early intracellular development but failed to tackle <em>C. parvum</em> growth when introduced at 30 h post infection. The present work introduces a new family of squaramide-derived IMPDH inhibitors and also interrogates the need to standardise commonly accepted protocols used for assessing anti-cryptosporidial drug activity.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100592"},"PeriodicalIF":4.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898678","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":"Ursolic acid induces apoptosis and disrupts host-parasite interactions in Theileria annulata-infected cells","authors":"Sakshi Singh , Madhusmita Subudhi , Vengatachala Moorthy A , Akash Suresh , Paresh Sharma","doi":"10.1016/j.ijpddr.2025.100593","DOIUrl":"10.1016/j.ijpddr.2025.100593","url":null,"abstract":"<div><div>This study explores the anti-proliferative and anti-parasitic properties of ursolic acid (UA) in <em>Theileria annulata</em>-infected bovine (TA) cells. Dose-response analyses determined an IC<sub>50</sub> value of approximately 5 μg/mL for UA, demonstrating selective cytotoxicity toward infected cells with minimal impact on healthy cells. UA treatment induced pronounced morphological alterations and apoptosis in TA cells, as evidenced by light microscopy and a time-dependent increase in cell mortality. Notably, UA exhibited consistent efficacy against both buparvaquone (BPQ)-sensitive and BPQ-resistant TA cell lines, highlighting its broad-spectrum anti-parasitic potential. Mechanistic investigations revealed that UA triggers DNA damage, elevates reactive oxygen species (ROS) levels, disrupts mitochondrial function, and induces sub-G1 phase arrest, culminating in apoptosis primarily via the intrinsic pathway. Mass spectrometry-based proteomic profiling identified significant perturbations in host cell pathways, including DNA repair mechanisms, cell cycle regulation, and signaling networks, alongside direct interference with parasite metabolic processes. Western blot analysis further confirmed UA-mediated modulation of host cell signaling pathways and chromatin organization. Given the rising incidence of drug-resistant <em>T. annulata</em> strains, the development of novel therapeutic strategies is imperative. These findings highlight UA's multifaceted mechanism of action, targeting both parasitic and host cellular processes, and position it as a promising candidate for the treatment of bovine theileriosis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100593"},"PeriodicalIF":4.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860023","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}
Kaylee R. Kipp , Elizabeth M. Redman , Joe L. Luksovsky , Dani Claussen , John S. Gilleard , Guilherme G. Verocai
{"title":"High frequency of benzimidazole resistance polymorphisms and age-class differences in trichostrongyle nematodes of ranched bison from the south-central United States","authors":"Kaylee R. Kipp , Elizabeth M. Redman , Joe L. Luksovsky , Dani Claussen , John S. Gilleard , Guilherme G. Verocai","doi":"10.1016/j.ijpddr.2025.100594","DOIUrl":"10.1016/j.ijpddr.2025.100594","url":null,"abstract":"<div><div>Bison production is a growing sector of the United States agriculture, with more consumers choosing bison products. Commercial bison are kept on smaller pastures and treated with anthelmintics for gastrointestinal nematodes (GIN) to maintain production. However, there is a lack of information regarding the GIN parasite communities in ranched bison or the extent of their resistance to anthelmintics. Our objectives were: i) to determine the GIN species present and the extent of resistance to the benzimidazole drug class in commercial bison herds in the southern US and ii) to assess age class differences in GIN species composition and BZ resistance. Composite coprocultures from bison in Texas (<em>n</em> = 14) and Oklahoma (<em>n</em> = 2), and individual bison of different age classes from a single ranch in central Texas (<em>n</em> = 43) were analyzed using ITS2 rDNA nemabiome metabarcoding to determine the trichostrongylid species composition. For both the composite and individual samples, the most common trichostrongylid species found were <em>Haemonchus contortus, Haemonchus placei</em>, and <em>Ostertagia ostertagi</em>. Among the known canonical isotype-1 β-tubulin BZ resistance polymorphisms (at codons 200, 198, 167), the 200Y (TTC > T<u>A</u>C) substitution was the most widespread across the two southern states, with a prevalence of 81.3 %. Other polymorphisms, such as 167Y (TTC > T<u>A</u>C) and 198L (GAA > <u>TT</u>A), were also detected, and both had prevalences of 62.5 %. <em>Ostertagia ostertagi</em> was found to have very high frequencies (overall mean frequency = 62.6 %; range = 28.3–100 %) of the 200Y (TTC > T<u>A</u>C) polymorphism in all age classes sampled. Overall, benzimidazole resistance polymorphisms were found at moderate to high frequency in the three major economically important GIN species in ranched bison in Texas and Oklahoma, suggesting a potential widespread distribution of benzimidazole resistance polymorphisms in the southern United States. This work has important implications for all other grazing livestock and illustrates the importance of early detection of anthelmintic resistance and the need for mitigation strategies.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100594"},"PeriodicalIF":4.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838341","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}
Fernanda G. Fumuso , Jason A. Clement , Matthew J. Todd , Roberta M. O'Connor
{"title":"Tartrolon E rapidly blocks Toxoplasma gondii capacity to invade host cells","authors":"Fernanda G. Fumuso , Jason A. Clement , Matthew J. Todd , Roberta M. O'Connor","doi":"10.1016/j.ijpddr.2025.100591","DOIUrl":"10.1016/j.ijpddr.2025.100591","url":null,"abstract":"<div><div>Toxoplasmosis is a worldwide parasitic disease caused by the apicomplexan <em>Toxoplasma gondii</em>. Severe neurological illness occurs in immunosuppressed patients, and congenital disorders can follow transplacental primo infection during pregnancy. New effective antiparasitic drugs are needed since chronic cystic stages are resistant to current available treatments, and some of the congenital infections are unresponsive to available therapeutics. Tartrolon E (trtE) is a marine secondary metabolite that has high selectivity against human and animal apicomplexan parasites including <em>T. gondii</em>, <em>Cryptosporidium parvum</em> and <em>Plasmodium falciparum</em>. We evaluated the effect of the compound on extracellular tachyzoite viability, morphology, membrane permeability and its ability to block host cell attachment and/or invasion. While 80 % of <em>T. gondii</em> infective capacity is blocked after only 30 min of compound treatment, parasite viability, morphology, membrane integrity and host cell attachment were unaffected until after 4 h of treatment. These effects were irreversible when parasites were allowed to infect host cells after trtE treatment. Drug exposure for more than 4 h significantly affected tachyzoite survival and altered parasite morphology. The mechanism of action of trtE is still unknown but includes blocking parasite invasion processes. Further research is needed to determine the molecular target of trtE to further progress the compound as an antiparasitic candidate.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100591"},"PeriodicalIF":4.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830062","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}
Dave Leathwick, Peter Green, Charlotte Bouchet, Alex Chambers, Tania Waghorn, Christian Sauermann
{"title":"The faecal egg count reduction test: Will identification of larvae to species improve its utility?","authors":"Dave Leathwick, Peter Green, Charlotte Bouchet, Alex Chambers, Tania Waghorn, Christian Sauermann","doi":"10.1016/j.ijpddr.2025.100589","DOIUrl":"10.1016/j.ijpddr.2025.100589","url":null,"abstract":"<div><div>In the faecal egg count reduction test, visual identification of larvae cultured from faeces enables the egg counts to be apportioned to species/genera, resulting in a more accurate test. However, morphology cannot reliably differentiate some species meaning that, in some cases, efficacy can only be estimated at the genus or species-complex level. We investigated the benefits of identifying larvae to species using DNA to determine how often this would alter the diagnosis of resistance and whether increasing the number of larvae identified would alter the repeatability of an efficacy estimate.</div><div>Data on faecal nematode egg counts and the corresponding larval species mixes were acquired from tests conducted on commercial sheep farms. The proportion of each species present in faecal culture was determined using DNA. Efficacy was then compared for individual species and for those genera/species complexes which cannot reliably be differentiated visually. The proportion of each species present was subsequently resampled 10,000 times (repeated random sampling) and efficacy recalculated to produce the median efficacy, along with the 5 % and 95 % simulation percentiles. Subsequently, the number of larvae sampled to determine the species mix in each sample was varied from 50 to 6400 and the process repeated.</div><div>Of 152 comparisons of efficacy, 25 % of cases where genus-level identification resulted in a finding of ‘susceptible’ for that category, species-level identification returned at least one diagnosis of ‘resistant’ i.e., genus-level identification resulted in a 25 % false negative diagnosis.</div><div>When the number of larvae sampled for species identification was low (<400) variation in efficacy estimates was high, however, as sample size increased the confidence interval around the efficacy estimate decreased.</div><div>The results indicate that identifying large numbers of larvae to species using DNA has the potential to increase the accuracy and confidence in efficacy estimates achieved using the faecal egg count reduction test.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100589"},"PeriodicalIF":4.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726167","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}
Zachary Caterer , Rachel V. Horejsi , Carly Weber , Blake Mathisen , Chase N. Nelson , Maggie Bagatta , Ireland Coughlin , Megan Wettstein , Ankit Kulshrestha , Hui Siang Benjamin Lee , Leonardo R. Nunn , Mostafa Zamanian , Nicolas J. Wheeler
{"title":"A graphical user interface for wrmXpress 2.0 streamlines helminth phenotypic screening","authors":"Zachary Caterer , Rachel V. Horejsi , Carly Weber , Blake Mathisen , Chase N. Nelson , Maggie Bagatta , Ireland Coughlin , Megan Wettstein , Ankit Kulshrestha , Hui Siang Benjamin Lee , Leonardo R. Nunn , Mostafa Zamanian , Nicolas J. Wheeler","doi":"10.1016/j.ijpddr.2025.100588","DOIUrl":"10.1016/j.ijpddr.2025.100588","url":null,"abstract":"<div><div>Image-based phenotypic screening is a fundamental technique used to better understand the basic biology of helminths and advance discovery of new anthelmintics. Miniaturization of screening platforms and automated microscopy have led to a surge in imaging data and necessitated software to organize and analyze these data. Traditionally, these analyses are performed remotely on high-performance computers, often requiring an understanding of a command line interface (CLI) and the ability to write scripts to control the software or job scheduler. Requiring access to specialized computing equipment and advanced computational skills raises the barrier to entry for these sorts of studies. The development of efficient, performant computer and graphical processing units for personal computers and cheaper imaging solutions has made the requirement of remote servers superfluous for many small to medium-scale screens, but most analytical software still require interaction with a CLI. To democratize the analysis of image-based phenotypic screens, we have developed a graphical user interface (GUI) for wrmXpress, a tool that integrates many popular computational pipelines for analyzing imaging data of parasitic and free-living worms. The GUI operates on any personal computer using the operating system's native web browser, allowing users to configure and run analyses using a point-and-click approach. Containerization of the application eliminates the need to install specialized programming libraries and dependencies, further increasing the ease of use. GUI development required a substantial reorganization of the wrmXpress backend codebase, which allowed for the addition of a new pipeline for high-resolution tracking of worm behavior, and we demonstrate its functionality by showing that praziquantel modulates the behavior of <em>Schistosoma mansoni</em> miracidia. These advances make cutting-edge analyses of image-based phenotyping of worms more equitable and accessible.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100588"},"PeriodicalIF":4.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678955","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}