Article
Immunology
Ragab M. Fereig, Hanan H. Abdelbaky, Yoshifumi Nishikawa
Summary: This study evaluated the potential of recombinant N. caninum dense granule protein 6 fused with glutathione-S-transferase (NcGRA6+GST) as a vaccine candidate against neosporosis in a pregnant mouse model. The results showed that NcGRA6+GST partially protected the dams and offspring from N. caninum infection during pregnancy, with higher survival rates and lower parasite burden. This suggests the efficacy of recombinant NcGRA6 for interrupting the vertical transmission of N. caninum in mice by reducing the severity of infections in dams and offspring.
Article
Veterinary Sciences
Guili Yu, Wei Liang, Qiankun Yang, Jinxin Wang, Yu Wang, Tianmeng Zhang, Xiao Zhang, Hui Fan, Panpan Zhao, Lili Cao, Jingquan Dong
Summary: Neospora caninum's dense granule proteins, including GRA4, exhibit potential as vaccine candidates, triggering protective immune responses and significantly improving survival rates and reducing parasite burden.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Review
Oncology
Suhui Yang, Chanel Jackson, Eduard Karapetyan, Pranabananda Dutta, Dulcie Kermah, Yong Wu, Yanyuan Wu, John Schloss, Jaydutt V. Vadgama
Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, while protein disulfide isomerase (PDI) has been identified as a potential therapeutic target due to its role in tumor progression. Selective blockade of PDI can induce apoptosis through sustained activation of UPR pathways. Future research should focus on the roles of PDI in highly metastatic breast cancers like TNBC.
Article
Biochemistry & Molecular Biology
Pingyu Yan, Zhiyuan Zou, Shiyao Zhang, Rui Wang, Tingting Niu, Xia Zhang, Defu Liu, Xuejie Zhou, Alan K. Chang, Nathaniel G. N. Milton, Gary W. Jones, Jianwei He
Summary: The study investigated the binding between Pichia pastoris PDI and amyloidogenic proteins, revealing multiple binding modes between PDI and its substrates, suggesting different specificities and affinities. PDI may eliminate the need for misfolded proteins to be localized in ER-associated compartments by promoting protein folding.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Parasitology
Congshan Yang, Chenrong Wang, Jing Liu, Qun Liu
Summary: This study utilized BioID technology to identify novel components of Neospora caninum dense granules, shedding light on the biological functions of GRA proteins. 11 new GRA proteins were confirmed to be localized in the Nc1 strain.
PARASITES & VECTORS
(2021)
Article
Biochemistry & Molecular Biology
Renato Simoes Gaspar, Jonathan M. Gibbins
Summary: Protein disulfide isomerase (PDI) and sibling proteins play essential roles in thrombus formation by influencing protein folding and function at the cell surface. Thiol isomerase targets have been identified, demonstrating their significance in regulating thrombosis.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Veterinary Sciences
Jingquan Dong, Nan Zhang, Panpan Zhao, Jianhua Li, Lili Cao, Xiaocen Wang, Xin Li, Ju Yang, Xichen Zhang, Pengtao Gong
Summary: This study investigated the NcGRA2 protein in Neospora caninum using various methods, revealing its colocalization with NcGRA6 and constructing a Delta NcGRA2 strain to explore its virulence. The results demonstrated that the Delta NcGRA2 strain exhibited smaller plaques, slower intracellular growth in vitro, and lower parasite burden with mild histopathological changes in vivo. These findings suggest that NcGRA2 weakens N. caninum virulence by affecting proliferation, providing insights for further research on protein functions in N. caninum.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Xingju Song, Xu Yang, Zhu Ying, Heng Zhang, Jing Liu, Qun Liu
Summary: GRX S14 and GRX C5 were confirmed to play a coordinated role in the growth of Neospora caninum parasites, with double knockout affecting reproductive capacity and downregulating certain proteins. However, the redox balance in parasite cells was not significantly affected by the absence of grx S14 and grx C5.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Monica L. Mazuz, Benjamin Leibovitz, Igor Savitsky, Elena Blinder, Daniel Yasur-Landau, Yaniv Lavon, Binyamin Sharir, Sharon Tirosh-Levy
Summary: Vaccination with frozen live Neospora caninum tachyzoites was found to reduce abortion rates in naturally infected seropositive pregnant dairy dams, particularly in cows with high antibody titers. The vaccine efficacy varied among different farms, but overall, the frozen live vaccination may be an effective method to control neosporosis in cattle.
Article
Parasitology
Laura Rico-San Roman, Rafael Amieva, Pilar Horcajo, Marta Garcia-Sanchez, Ivan Pastor-Fernandez, Luis Miguel Ortega-Mora, Esther Collantes-Fernandez
Summary: Bovine neosporosis is a major cause of reproductive failure in cattle worldwide, but the molecular basis and mechanisms underlying its virulence are mostly unknown. This study investigated the role of NcGRA7 and NcROP40 in bovine target cells using in vitro models. The results showed that the mutant parasites had decreased proliferation capacity in bovine monocyte-derived macrophages but no differences in bovine trophoblast. These proteins may be involved in manipulating innate immune defense mechanisms against neosporosis. The study highlights the usefulness of the bovine macrophage model and opens up opportunities for future research.
VETERINARY PARASITOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mirva J. Saaranen, Heli Alanen, Kirsi E. H. Salo, Emmanuel Nji, Pekka Karkkainen, Constanze Schmotz, Lloyd W. Ruddock
Summary: Proteins in the thioredoxin superfamily, such as protein disulfide isomerase (PDI) and glutaredoxins, have similar structures and catalytic mechanisms. PDI uses glutathione for oxidation/reduction in vitro, while glutaredoxins have a high affinity for glutathione. Mutating the active site of PDI to a more glutaredoxin-like motif increases its reactivity with glutathione.
Review
Immunology
Ana Elisa Del'Arco, Deivison Silva Argolo, Gilles Guillemin, Maria de Fatima Dias Costa, Silvia Lima Costa, Alexandre Moraes Pinheiro
Summary: Neuroinflammation is a common feature in neurological disorders and can be both neuroprotective and neurotoxic. The kynurenine pathway, involved in immune regulation, neuroprotection, and neurotoxicity, is frequently activated during neuroinflammation. Studying the kynurenine pathway in the context of Neospora caninum infection can provide insights into its role in the neuroinflammatory response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Abdul Burhan Khan, Urfi Siddiqui, Sana Fatima, Ahmed Abdur Rehman, Mohamad Aman Jairajpuri
Summary: Current antithrombotic drugs have drawbacks, prompting the search for new and cheaper alternatives. This study found that naringin has high binding affinity for PDI, altering its conformation and activity, and thereby affecting blood coagulation rates.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Analytical
Ying-Jie Tang, Shan He, Xiao-Feng Guo, Hong Wang
Summary: The endoplasmic reticulum (ER) is a critical organelle in cells involved in protein synthesis, folding, and transport, with redox balance being essential for its normal function. A newly designed fluorescent probe N-Se showed selective and rapid response to ClO- with reversible detection capability, allowing real-time monitoring of redox status in the ER through changes in fluorescence intensity.
Article
Biochemistry & Molecular Biology
Hong Jiang, Pratik Thapa, Yanning Hao, Na Ding, Aziza Alshahrani, Qiou Wei
Summary: This review explores the association between diabetes and cancer, with a focus on the role of the protein disulfide isomerase (PDI) family. Understanding the molecular contribution of individual PDIs in specific diseases may provide insights for the development of targeted therapeutics.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Joachim Muller, Nicoleta Anghel, Dennis Imhof, Kai Hanggeli, Anne-Christine Uldry, Sophie Braga-Lagache, Manfred Heller, Kayode K. Ojo, Luis-Miguel Ortega-Mora, Wesley C. Van Voorhis, Andrew Hemphill
Summary: Neospora caninum, closely related to Toxoplasma gondii, is a parasite that can cause fetal malformations in livestock. The development of calcium-dependent protein kinase 1 inhibitors has shown promise in treating neosporosis. However, some of these inhibitors have adverse effects on fertility in pregnant mouse models and cause embryonic malformations in zebrafish models. Through affinity chromatography and mass spectrometry, it has been found that BKI-1748 interacts not only with specific targets in apicomplexans but also with targets in other eukaryotes, indicating involvement in common essential pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lorenz Ulrich, Nico Joel Halwe, Adriano Taddeo, Nadine Ebert, Jacob Schoen, Christelle Devisme, Bettina Salome Trueb, Bernd Hoffmann, Manon Wider, Xiaoyu Fan, Meriem Bekliz, Manel Essaidi-Laziosi, Marie Luisa Schmidt, Daniela Niemeyer, Victor Max Corman, Anna Kraft, Aurelie Godel, Laura Laloli, Jenna N. Kelly, Brenda M. Calderon, Angele Breithaupt, Claudia Wylezich, Ines Berenguer Veiga, Mitra Gultom, Sarah Osman, Bin Zhou, Kenneth Adea, Benjamin Meyer, Christiane S. Eberhardt, Lisa Thomann, Monika Gsell, Fabien Labroussaa, Joerg Jores, Artur Summerfield, Christian Drosten, Isabella Anne Eckerle, David E. Wentworth, Ronald Dijkman, Donata Hoffmann, Volker Thiel, Martin Beer, Charaf Benarafa
Summary: Experimental assessments of major VOCs show that Alpha and Beta variants have a higher affinity for the human ACE2 receptor compared to the progenitor variant. Competition experiments demonstrate that Alpha has a clear fitness advantage over wt-S-614G in ferrets and mouse models.
Article
Microbiology
Peter Kuhnert, Isabelle Brodard, Sabine Bock, Andrew Hemphill, Hatice Akarsu, Andreas Engelhardt, Peter Kutzer
Summary: Seven bacterial strains isolated from bovine endocarditis were classified into a new genus within the family Neisseriaceae, distinct from established genera. Whole genome sequence analysis and MALDI-TOF MS spectra analysis were effective methods for identification.
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
(2022)
Article
Parasitology
Yang Zheng, Joachim Mueller, Stefan Kunz, Marco Siderius, Louis Maes, Guy Caljon, Norbert Mueller, Andrew Hemphill, Geert Jan Sterk, Rob Leurs
Summary: By combining structural elements of phosphodiesterase inhibitors with a nitroimidazole scaffold, the study aimed to improve antiparasitic efficacy by generating nitrosative stress.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Immunology
Azadeh Nasuhidehnavi, Yanlin Zhao, Ankita Punetha, Andrew Hemphill, Hong Li, Tyler J. Bechtel, Theresa Rager, Bingcong Xiong, Vasileios Petrou, Marc-Jan Gubbels, Eranthie Weerapana, George S. Yap
Summary: The host cell surface receptor, basigin, and its related immunoglobulin family members play an important role in mediating the attachment of Toxoplasma gondii to host cells.
INFECTION AND IMMUNITY
(2022)
Article
Veterinary Sciences
Dennis Imhof, William Robert Pownall, Carling Schlange, Camille Monney, Luis-Miguel Ortega-Mora, Kayode K. Ojo, Wesley C. Van Voorhis, Anna Oevermann, Andrew Hemphill
Summary: This study investigated the safety and efficacy of a combined vaccination-drug treatment approach in a pregnant neosporosis mouse model. The results showed that the combination treatment was more effective in reducing infection and improving pup survival compared to vaccination or drug treatment alone. Further evaluation is recommended.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Veterinary Sciences
Sheena Chaudhry, Raphael Zurbriggen, Matias Preza, Tobias Kampfer, Marc Kaethner, Roman Memedovski, Nathalie Scorrano, Andrew Hemphill, Joseph Stone Doggett, Britta Lundstrom-Stadelmann
Summary: Alveolar echinococcosis, caused by the zoonotic parasite Echinococcus multilocularis, could potentially be treated through a novel approach targeting the mitochondrial energy metabolism of the parasite, specifically the oxidative phosphorylation and the anaerobic malate dismutation pathways.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Joachim Mueller, Ghalia Boubaker, Dennis Imhof, Kai Haenggeli, Noe Haudenschild, Anne-Christine Uldry, Sophie Braga-Lagache, Manfred Heller, Luis-Miguel Ortega-Mora, Andrew Hemphill
Summary: Leucinostatins are antimicrobial peptides that have a broad range of activities. In this study, a derivative peptide called 6027 was tested for its activity against Toxoplasma gondii, a parasitic organism. While effective in vitro, the application of peptide 6027 in mice infected with T. gondii worsened the infection. Peptide 6027 also affected the viability of mouse splenocytes. Through differential affinity chromatography and mass spectrometry, common targets for peptide 6027 were identified in both T. gondii and mouse spleen extracts. This method can be a useful way to identify drug targets in pathogens and hosts.
Article
Immunology
Monireh Khordadmehr, Alireza Sazmand, Pardis Almasi, Parisa Shahbazi, Vahidreza Ranjbar, Domenico Otranto, Andrew Hemphill
Summary: This study provides an overview of the prevalence and exposure to tissue cyst-forming apicomplexan parasites in Iranian domestic rock pigeons through molecular, serological, and histopathological examination. The results demonstrate that pigeons in Iran are infected, particularly with T. gondii, and suggest the need for control strategies to minimize the risk of infection in both pigeons and humans.
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Oksana Desiatkina, Martin Moesching, Nicoleta Anghel, Ghalia Boubaker, Yosra Amdouni, Andrew Hemphill, Julien Furrer, Emilia Paunescu
Summary: A library of nucleobase-tethered trithiolato-bridged dinuclear ruthenium(II)-arene conjugates was synthesized and evaluated for their anti-Toxoplasma activity. Two promising compounds were identified, which exhibited low toxicity against host cells and have potential as treatment options.
Article
Biochemistry & Molecular Biology
Isabelle Holzer, Oksana Desiatkina, Nicoleta Anghel, Serena K. K. Johns, Ghalia Boubaker, Andrew Hemphill, Julien Furrer, Emilia Paunescu
Summary: Eight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized and evaluated for their activity against transgenic T. gondii tachyzoites. Seven conjugates strongly inhibited parasite proliferation while maintaining HFF viability. Two galactose-based conjugates (23 and 26) exhibited low IC50 values and reduced toxicity compared to the non-modified complexes.
Article
Microbiology
Chandra Ramakrishnan, Aarti Krishnan, Samuel Francisco, Marc W. Schmid, Giancarlo Russo, Alexandre Leitao, Andrew Hemphill, Dominique Soldati-Favre, Adrian B. Hehl
Summary: This study presents a comparative analysis of gene expression in different stages of the Besnoitia besnoiti parasite, and discovers its potential as a model organism for studying the evolution of tissue cysts and the biology of related parasites. This research contributes to a deeper understanding of the biology of besnoitiosis in cattle and other tissue-cyst forming parasites.
Article
Immunology
Dennis Imhof, William Pownall, Kai Pascal Alexander Hanggeli, Camille Monney, Laura Rico-San Roman, Luis-Miguel Ortega-Mora, Franck Forterre, Anna Oevermann, Andrew Hemphill
Summary: In this study, a modified version of the attenuated Listeria monocytogenes vaccine vector Lm3Dx_NcSAG1 was tested for its efficacy in a pregnant neosporosis mouse model. Multivalent vaccines were generated by inserting gra7 and/or rop2 genes into Lm3Dx_NcSAG1. Immunization with Lm3Dx_NcSAG1 and Lm3Dx_NcSAG1_NcGRA7_NcROP2 resulted in the highest postnatal pup survival rate and protection against vertical transmission and CNS infection.
Article
Biochemistry & Molecular Biology
Kai Pascal Alexander Hanggeli, Andrew Hemphill, Norbert Muller, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Joachim Muller, Ghalia Boubaker
Summary: Gene knock-out using CRISPR-Cas9 is a useful tool to identify gene functions in T. gondii and other model organisms. Previous studies have shown that knocking out a gene can also affect the expression of other genes. Therefore, caution should be taken when studying the relationship between specific phenotypes and the knock-out of a particular gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Parasitology
Joachim Mueller, Carling Schlange, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Richard K. Haynes, Andrew Hemphill
Summary: Artemisinin and its amino-artemisinin derivatives are potent antimalarials and exhibit different mechanisms of action against Plasmodium and T. gondii. The amino-artemisinins are effective in vitro against non-heme-degrading apicomplexan parasites including T. gondii. However, T. gondii strains readily adapt to increased concentrations of these compounds, resulting in the development of resistant strains.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2023)