Frontiers in parasitologyPub Date : 2023-07-27eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1258999
María V Periago, Roberto Chuit
{"title":"Editorial: New opportunities for diagnosis and control of Chagas Disease to reach the 2030 goals for elimination.","authors":"María V Periago, Roberto Chuit","doi":"10.3389/fpara.2023.1258999","DOIUrl":"10.3389/fpara.2023.1258999","url":null,"abstract":"","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1258999"},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48503451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-07-24eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1195646
Roberto Chuit, Laura Antonietti, Roberto Nicolás Agüero, Gabriela Badino Varela, Oscar Daniel Mordini, Emilce Alemandri, Marcelo Abril, Miguel Días, Zaida E Yadón, Hugo Pizzi, Rogelio Pizzi
{"title":"Diagnosis and management of chagasic cardiomyopathy patients in several institutions in Argentina.","authors":"Roberto Chuit, Laura Antonietti, Roberto Nicolás Agüero, Gabriela Badino Varela, Oscar Daniel Mordini, Emilce Alemandri, Marcelo Abril, Miguel Días, Zaida E Yadón, Hugo Pizzi, Rogelio Pizzi","doi":"10.3389/fpara.2023.1195646","DOIUrl":"10.3389/fpara.2023.1195646","url":null,"abstract":"<p><strong>Introduction: </strong>According to estimates by the World Health Organization, the infection and disease caused by the protozoan parasite <i>Trypanosoma cruzi</i> affects almost 6 million people, and more than 1 million suffer chagasic cardiomyopathy (Ch-CMP). It is estimated that 376,000 of these individuals live in Argentina. This study describes the characteristics and medical management of individuals with Ch-CMP in Argentina.</p><p><strong>Methods: </strong>This is a descriptive, retrospective, cross-sectional study on the diagnosis and clinical and therapeutic evaluation of patients with Ch-MCP using historical records collected from different medical institutions in the country between 1 January 2018 and 30 June 2021.</p><p><strong>Results: </strong>During this period, 652 patients (mean age 61.2 years ± 12.9) were included, with women accounting for 60.3% of the sample. The diagnosis of cardiac insufficiency was 36.0% and 64.4% had arrhythmias. The most common cardiovascular risk factors detected were arterial hypertension (69.5%), smoking (56.6%), and diabetes (20.9%). Less than half of the subjects (45.4%) had been studied by electrocardiogram (ECG), chest X-ray, and echocardiogram. ECG studies showed conduction disorders (38.8%), left ventricular hypertrophy (28.1%), ventricular extrasystoles (22.0%), complete right bundle branch block (8.6%), and atrioventricular block (2.6%). According to the Kuschnir classification, 21.4% of the study subjects were in Grade 3.</p><p><strong>Conclusions: </strong>The patients included in the study had a similar clinical presentation and history of the disease to those published in other studies. When evaluating the medical practices, we found that patients were inadequately studied. Although it is difficult to estimate the fraction of the total number of patients represented by the present study, the study allowed us to establish that the care received by patients was not adequate.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1195646"},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49017695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-07-06eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1214136
Jenna M Lane, Tara P Brosschot, Dominique M Gatti, Courtney M Gauthier, Katherine M Lawrence, Victoria Pluzhnikova, Lisa A Reynolds
{"title":"Chronic small intestinal helminth infection perturbs bile acid homeostasis and disrupts bile acid signaling in the murine small intestine.","authors":"Jenna M Lane, Tara P Brosschot, Dominique M Gatti, Courtney M Gauthier, Katherine M Lawrence, Victoria Pluzhnikova, Lisa A Reynolds","doi":"10.3389/fpara.2023.1214136","DOIUrl":"10.3389/fpara.2023.1214136","url":null,"abstract":"<p><p>Intestinal helminths have evolved an abundance of immunomodulatory mechanisms to ensure long-lived infections in mammalian hosts. To manipulate mammalian immune responses helminths can directly produce immunomodulatory molecules, but helminth infection can also elicit functional changes in the intestinal microbiome which can impact immune functioning. Here we examined how bile acids (BA)s, a group of host-produced, microbiota-modified immunomodulatory metabolites, were altered in abundance and composition during a murine small intestinal helminth infection. We found that murine helminth infection resulted in consistently reduced concentrations of specific taurine-conjugated primary BAs (T-α-MCA and T-CDCA) in the small intestinal luminal contents of mice. BA transporters facilitate the uptake of BAs from the small intestinal lumen, allowing BAs to engage with nuclear BA receptors, and helminth infected mice showed reduced expression of genes encoding basal BA transporters in the small intestine. Finally, we report that there is reduced signaling through the nuclear BA receptor FXR in both the proximal small intestine and ileum of mice during small intestinal helminth infection. Together, our data reveal disruptions to BA homeostasis and signaling in the small intestine during helminth infection. As BAs are known to impact many aspects of mucosal physiology and immunity, examining the functional consequences of BA disruptions during helminth infection will be an important avenue for future research.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"1 1","pages":"1214136"},"PeriodicalIF":0.0,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42359260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-06-19eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1189872
Danica Lennox-Bulow, Luke Becker, Alex Loukas, Jamie Seymour, Michael Smout
{"title":"Optimizing the xWORM assay for monitoring hookworm larvae motility.","authors":"Danica Lennox-Bulow, Luke Becker, Alex Loukas, Jamie Seymour, Michael Smout","doi":"10.3389/fpara.2023.1189872","DOIUrl":"10.3389/fpara.2023.1189872","url":null,"abstract":"<p><p>Parasitic worms (helminths) infect almost all taxa across the animal kingdom, and pose significant challenges to public health and economies, particularly in developing countries. To address this problem, researchers have developed various tools to measure the motility and viability of helminths. However, the conditions used in anthelmintic screening assays are often not optimized, and can vary considerably between research teams. These unoptimized conditions may impact novel drug screens, as little is known about the effects of different conditions on the health of the target parasites. To improve future research, this study determined the effects of key assay parameters including, media type, media concentration, in-well parasite density, and assay duration on the infective third-stage larva (L3) of two types of hookworms, namely <i>Nippostrongylus brasiliensis</i> in rodents, and <i>Necator americanus</i> in humans. Conditions were screened over several days using the xCELLigence worm real-time motility assay (xWORM); a real-time impedance-based helminth motility assay using the xCELLigence system with 96-well microplates. While results varied depending on the species and media used, the study found that 500-1,000 L3/200-µL and a media concentration of 3.13-25% generally produced good to excellent assay conditions. The findings of this study can guide the future selection of xWORM assay parameters for novel drug trials involving these parasite species and serve as a suggested model for optimizing trial conditions for alternative parasite targets and assays.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1189872"},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44157099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-06-15eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1162697
Viraj Muthye, James D Wasmuth
{"title":"Proteome-wide comparison of tertiary protein structures reveals molecular mimicry in <i>Plasmodium</i>-human interactions.","authors":"Viraj Muthye, James D Wasmuth","doi":"10.3389/fpara.2023.1162697","DOIUrl":"10.3389/fpara.2023.1162697","url":null,"abstract":"<p><strong>Introduction: </strong>Molecular mimicry is a strategy used by parasites to evade the host's immune system and facilitate transmission to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, recent advances in the prediction of tertiary structural models, led by Deepmind's AlphaFold, enable the comparison of thousands of proteins from parasites and their hosts at the structural level, allowing for the identification of more mimics. Here, we present the first proteome-level search for tertiary structure similarity between proteins from <i>Plasmodium falciparum</i>, a malaria-causing parasite, and humans.</p><p><strong>Methods: </strong>We assembled a database of experimentally-characterized protein tertiary structures (from the Protein Data Bank) and AlphaFold-generated protein tertiary structures from <i>P. falciparum</i>, human, and 15 negative control species, <i>i.e</i>., species not infected by <i>P. falciparum</i>. We aligned human and control structures to the parasite structures using Foldseek.</p><p><strong>Results: </strong>We identified molecular mimicry in three proteins that have been previously proposed as mediators of <i>Plasmodium</i>-human interactions. By extending this approach to all <i>P. falciparum</i> proteins, we identified an additional 41 potential mimics that are supported by additional experimental data.</p><p><strong>Discussion: </strong>Our findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1162697"},"PeriodicalIF":0.0,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43085345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-06-02eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1186149
Antonio Bosco, Antonello Prigioniero, Alessandra Falzarano, Maria Paola Maurelli, Laura Rinaldi, Giuseppe Cringoli, Giovanni Quaranta, Salvatore Claps, Rosaria Sciarrillo, Carmine Guarino, Pierpaolo Scarano
{"title":"Use of perennial plants in the fight against gastrointestinal nematodes of sheep.","authors":"Antonio Bosco, Antonello Prigioniero, Alessandra Falzarano, Maria Paola Maurelli, Laura Rinaldi, Giuseppe Cringoli, Giovanni Quaranta, Salvatore Claps, Rosaria Sciarrillo, Carmine Guarino, Pierpaolo Scarano","doi":"10.3389/fpara.2023.1186149","DOIUrl":"10.3389/fpara.2023.1186149","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal nematodes (GINs) are a serious problem in ruminant pastures worldwide. They generate production losses, from the point of view of both the food chain and animal mortality. This study provides preliminary results concerning the use of pasture plants in the Campania region (of southern Italy) to control GINs in sheep.</p><p><strong>Methods: </strong>Sixteen species of wild and cultivated perennial plants present in seminatural pastures were sampled. All species were extracted with the conventional maceration technique, using three different solvents (i.e., H<sub>2</sub>O, EtOH, and an EtOH:H<sub>2</sub>O (8:2) mixture) in order to extract different bioactive compounds. The total phenolic content (TPC; assessed <i>via</i> the Folin-Ciocȃlteu assay) of all extract samples was preliminarily characterized. Each sample was aliquoted across six different concentrations and an <i>in vitro</i> egg hatching test (EHT) was conducted to evaluate the ovicidal effect on sheep GINs.</p><p><strong>Results: </strong>The results indicated that <i>Cichorium intybus</i> L. and <i>Foeniculum vulgare</i> Mill. extracts greatly inhibited egg hatching within 48 hours of exposure, showing efficacy (≥ 62.6%) at the three higher concentrations when compared with the other plants.</p><p><strong>Conclusion: </strong>The use of extracts of wild and cultivated perennial plant species in pastures can be a valid alternative to the use of synthetic anthelmintic drugs, which can generate problems, such as anthelmintic resistance, in the long term. Looking forward, further <i>in vitro</i> studies that evaluate the <i>in vitro</i> effect of these extracts on ruminant cell cultures, and field application through <i>in vivo</i> studies, would likely confirm the results obtained from preliminary <i>in vitro</i> EHTs. All these studies should be aimed at evaluating the therapeutic potential and future applicability of specific plant cultures in pastures to achieve sustainable pest control.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1186149"},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46863612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-05-24eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1197956
Josephine Schlosser-Brandenburg, Ankur Midha, Robert M Mugo, Eric M Ndombi, George Gachara, Doris Njomo, Sebastian Rausch, Susanne Hartmann
{"title":"Infection with soil-transmitted helminths and their impact on coinfections.","authors":"Josephine Schlosser-Brandenburg, Ankur Midha, Robert M Mugo, Eric M Ndombi, George Gachara, Doris Njomo, Sebastian Rausch, Susanne Hartmann","doi":"10.3389/fpara.2023.1197956","DOIUrl":"10.3389/fpara.2023.1197956","url":null,"abstract":"<p><p>The most important soil-transmitted helminths (STHs) affecting humans are roundworms, whipworms, and hookworms, with a large proportion of the world's population infected with one or more of these intestinal parasites. On top of that, concurrent infections with several viruses, bacteria, protozoa, and other helminths such as trematodes are common in STH-endemic areas. STHs are potent immunomodulators, but knowledge about the effects of STH infection on the direction and extent of coinfections with other pathogens and <i>vice versa</i> is incomplete. By focusing on Kenya, a country where STH infections in humans are widespread, we provide an exemplary overview of the current prevalence of STH and co-occurring infections (e.g. with Human Immunodeficiency Virus, <i>Plasmodium falciparum</i>, <i>Giardia duodenalis</i> and <i>Schistosoma mansoni</i>). Using human data and complemented by experimental studies, we outline the immunomechanistic interactions of coinfections in both acutely STH transmigrated and chronically infected tissues, also highlighting their systemic nature. Depending on the coinfecting pathogen and immunological readout, STH infection may restrain, support, or even override the immune response to another pathogen. Furthermore, the timing of the particular infection and host susceptibility are decisive for the immunopathological consequences. Some examples demonstrated positive outcomes of STH coinfections, where the systemic effects of these helminths mitigate the damage caused by other pathogens. Nevertheless, the data available to date are rather unbalanced, as only a few studies have considered the effects of coinfection on the worm's life cycle and associated host immunity. These interactions are complex and depend largely on the context and biology of the coinfection, which can act in either direction, both to the benefit and detriment of the infected host.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1197956"},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48578080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-05-24eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1138375
Constanza Lopez-Albizu, Rocío Rivero, Griselda Ballering, Hector Freilij, María Soledad Santini, Margarita María Catalina Bisio
{"title":"Laboratory diagnosis of <i>Trypanosoma cruzi</i> infection: a narrative review.","authors":"Constanza Lopez-Albizu, Rocío Rivero, Griselda Ballering, Hector Freilij, María Soledad Santini, Margarita María Catalina Bisio","doi":"10.3389/fpara.2023.1138375","DOIUrl":"10.3389/fpara.2023.1138375","url":null,"abstract":"<p><p><i>Trypanosoma cruzi</i> infection, currently endemic in 21 countries, is a public health problem not only in the Americas but also in countries with Latin American migrants. However, it is estimated that two-thirds of people with Chagas disease currently live in urban areas and that only 10% of them are aware of it. This review summarizes the most important aspects of the diagnosis of human <i>T. cruzi</i> infection by describing the following aspects of clinical laboratory diagnosis: the most widely used tests available in Latin America and those expected to improve access to diagnosis of the affected population with their implementation; the advantages, disadvantages, and sensitivity of the tests in the different phases of infection; and their usefulness in the acute or chronic phases of infection and in the context of immunosuppression. In this way, we hope to contribute to broadening the knowledge about this prevalent infection in the Americas.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"2 1","pages":"1138375"},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41344544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-04-28eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1076759
Seynabou D Sene, Mariama N Pouye, Rafael Miyazawa Martins, Fatoumata Diallo, Khadidiatou Mangou, Amy K Bei, Alioune Barry, Oumar Faye, Oumar Ndiaye, Ousmane Faye, Amadou A Sall, Jose-Juan Lopez-Rubio, Alassane Mbengue
{"title":"Identification of an <i>in vitro</i> artemisinin-resistant <i>Plasmodium falciparum</i> kelch13 R515K mutant parasite in Senegal.","authors":"Seynabou D Sene, Mariama N Pouye, Rafael Miyazawa Martins, Fatoumata Diallo, Khadidiatou Mangou, Amy K Bei, Alioune Barry, Oumar Faye, Oumar Ndiaye, Ousmane Faye, Amadou A Sall, Jose-Juan Lopez-Rubio, Alassane Mbengue","doi":"10.3389/fpara.2023.1076759","DOIUrl":"10.3389/fpara.2023.1076759","url":null,"abstract":"<p><p>The emergence of artemisinin partial resistance (ART-r) in <i>Plasmodium falciparum</i> malaria parasites has substantially compromised the efficacy of antimalarial treatments across southeast Asia (SE Asia). The spread of ART-r within the African continent could jeopardize past progress made in reducing worldwide malaria burden. A clinical index malaria case was identified in Kaolack, Senegal with persistent fever after complete artesunate-amodiaquine (ASAQ) treatment. Fifteen malaria-infected blood samples were collected by Institut Pasteur Dakar's Senegalese sentinel surveillance system, from different healthcare centers surrounding the index case. We have identified one <i>Plasmodium falciparum</i> clinical isolate carrying R515K mutation in the artemisinin resistance gene PfKelch13. CRISPR-Cas9 genome editing was carried out and transgenic Pf3D7Pfkelch13<sup>R515K</sup> was tested for <i>in vitro</i> standard Ring-stage Survival Assay <i>(RSA</i> <sup>0-3hpi</sup>). Gene editing has confirmed that <i>PfKelch13<sup>R515K</sup></i> drove increased <i>in vitro</i> RSA<sup>0-3hpi</sup> value. In this article, we report the functional significance of PfKelch13<sup>R515K</sup> mutation in an African context.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"2 1","pages":"1076759"},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41684281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in parasitologyPub Date : 2023-04-27eCollection Date: 2023-01-01DOI: 10.3389/fpara.2023.1118284
Kayo Yamada, Ning Zhang, Farzana K Yaqub, Martin Zoltner, Mark C Field
{"title":"TUSK: a ubiquitin hydrolase complex modulating surface protein abundance in trypanosomes.","authors":"Kayo Yamada, Ning Zhang, Farzana K Yaqub, Martin Zoltner, Mark C Field","doi":"10.3389/fpara.2023.1118284","DOIUrl":"10.3389/fpara.2023.1118284","url":null,"abstract":"<p><p>Control of protein levels is vital to cellular homeostasis, for maintaining a steady state, to coordinate changes during differentiation and other roles. In African trypanosomes surface proteins contribute to immune evasion, drug sensitivity and environmental sensing. The trypanosome surface is dominated by the GPI-anchored variant surface glycoprotein, but additional GPI-anchored and <i>trans</i>-membrane domain proteins are present with known roles as nutrient receptors and signal transducers. The evolutionarily conserved deubiquitinase orthologs of Usp7 and Vdu1 in trypanosomes modulate abundance of many surface proteins, including the invariant surface glycoproteins, which have roles in immune evasion and drug sensitivity. Here we identify multiple trypanosome Skp1 paralogs and specifically a divergent paralog SkpZ. Affinity isolation and LCMSMS indicates that SkpZ forms a heterotrimeric complex with TbUsp7 and TbTpr86, a tetratricopeptide-repeat protein. Silencing SkpZ decreases TbUsp7 and TbTpr86 abundance, confirming a direct association. Further, SkpZ knockdown decreases the abundance of multiple <i>trans</i>-membrane domain (TMD) proteins but increases GPI-anchored surface protein levels. Hence, a heterotrimeric complex of TbTpr86, TbUsp7 and SkpZ (TUSK) regulates expression levels of a significant cohort of trypanosome surface proteins mediating coordination between TMD and GPI-anchored protein expression levels.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" ","pages":"1118284"},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47598059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}