Article
Multidisciplinary Sciences
Iti Saraav, Luisa Cervantes-Barragan, Philipp Olias, Yong Fu, Qiuling Wang, Leran Wang, Yi Wang, Matthias Mack, Megan T. Baldridge, Thaddeus Stappenbeck, Marco Colonna, L. David Sibley
Summary: Oral infection with Toxoplasma gondii exacerbates damage to the colon caused by chemical irritant and impairs wound healing by suppressing stem cell regeneration. Enhanced tissue damage is due to inflammatory monocytes releasing inflammatory mediators.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Food Science & Technology
Pablo-Jesus Marin-Garcia, Nuria Planas, Lola Llobat
Summary: This article reviews the detection methods, prevalence, and control measures of Toxoplasma gondii in the food industry. T. gondii is a common parasite that causes infection through food contamination, but standardized detection methods are currently lacking in the industry. The main detection methods include bioassays, cell culture, molecular and microscopic techniques, and serological methods. Due to the high prevalence of T. gondii in many food products, standardized detection methods and control measures are necessary.
Article
Immunology
Mohammad Mahdi Jafari, Zahra Azimzadeh Tabrizi, Mohammad Saaid Dayer, Nazanin Atieh Kazemi-Sefat, Mahshid Mohtashamifard, Rahimeh Mohseni, Atefeh Bagheri, Saeed Bahadory, Amir Karimipour-Saryazdi, Fatemeh Ghaffarifar
Summary: Toxoplasma gondii infection is associated with immune response, which can be used as prognosis markers. Immunotherapy has become a new approach for toxoplasmosis treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Parasitology
Jiaofeng Huang, Jiaolong Zheng, Bang Liu, Lingling Lu, Haicong Wu, Su Lin, Dongliang Li
Summary: This study found that Toxoplasma gondii infection is associated with higher mortality in the general population, and this association is related to age and sex. This suggests that Toxoplasma gondii infection may be an important public health issue.
PARASITES & VECTORS
(2022)
Article
Multidisciplinary Sciences
Syrian G. Sanchez, Emilie Bassot, Aude Cerutti, Hoa Mai Nguyen, Amel Aida, Nicolas Blanchard, Sebastien Besteiro
Summary: Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be serious when contracted during pregnancy, but can also be a threat for immunocompromised individuals. The study finds that targeting the apicoplast in bradyzoites, the latent form of the parasite, leads to a loss of long-term viability, suggesting the apicoplast as a potential therapeutic target.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Geriatrics & Gerontology
Hira Mohyuddin, Blanca Laffon, Joao P. Teixeira, Solange Costa, Armanda Teixeira-Gomes, Eduardo Pasaro, Niel Constantine, Aline Dagdag, Heidi K. Ortmeyer, Boris Tizenberg, Liubov Afram, Poyu Yen, Christopher Marano, Christopher A. Lowry, Andrew J. Hoisington, Jill A. Rachbeisel, Vanessa Valdiglesias, Carlota Lema-Arranz, Natalia Fernandez-Bertolez, Ana Maseda, Jose C. Millan-Calenti, Elizabeth J. Kovacs, Johanna M. Gostner, Dietmar Fuchs, Lisa A. Brenner, Laura Lorenzo-Lopez, Teodor T. Postolache
Summary: This study revealed an association between Toxoplasma gondii and frailty, but further research is needed for validation. Certain biomarkers related to inflammaging were associated with both Toxoplasma gondii and frailty, but they did not fully mediate the association between the two.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Immunology
Amy C. Schumacher, Lina Elbadawi, Traci DeSalvo, Anne Straily, Daniel Ajzenberg, David Letzer, Ellen Moldenhauer, Tammy L. Handly, Dolores Hill, Marie-Laure Darde, Christelle Pomares, Karine Passebosc-Faure, Kristine Bisgard, Carlos A. Gomez, Cindy Press, Stephanie Smiley, Jose G. Montoya, James J. Kazmierczak
Summary: In 2017, an outbreak of toxoplasmosis was linked to undercooked venison served at a retreat in Wisconsin. Most of the attendees experienced illness, with laboratory results showing atypical features for toxoplasmosis. The strain of T. gondii found in the venison was a unique genotype, highlighting the potential risks of consuming undercooked game meat in North America.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Thais Cabral Monica, Fernanda Evers, Beatriz Souza Lima Nino, Fernanda Pinto-Ferreira, Jose Wander Bregano, Mariana Ragassi Urbano, Guita Rubinsky-Elefant, Roberta Lemos Freire, Italmar Teodorico Navarro, Regina Mitsuka-Bregano
Summary: The study examined the seroprevalence and risk factors of toxoplasmosis and toxocariasis in schoolchildren in Jataizinho, Parana, revealing associations with factors such as the mother's education level, age, presence of cats in the household, income, and presence of dogs. There was also an association between the two zoonoses, highlighting the importance of implementing control measures to reduce the incidence and risks of sequelae in children.
TRANSBOUNDARY AND EMERGING DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Ragab M. Fereig, Yoshifumi Nishikawa
Summary: In this study, the cyto-nuclear and mitochondrial localization of TgPrx1 and TgPrx3 proteins in Toxoplasma gondii were revealed. Knocking out TgPrx1 and TgPrx3 genes in T. gondii resulted in decreased survival rate in mice infected with TgPrx3KO strain compared to TgPrx1KO and control strains. Additionally, TgPrx1KO and TgPrx3KO induced high levels of interferon gamma (IFN-gamma) and increased IL-6 and IL-12p40 production in infected mice and murine macrophages. These findings suggest that TgPrx3 may be a potential sub-unit vaccine candidate for controlling toxoplasmosis in susceptible humans and animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lokman Galal, Frederic Ariey, Meriadeg Ar Gouilh, Marie-Laure Darde, Azra Hamidovic, Franck Letourneur, Franck Prugnolle, Aurelien Mercier
Summary: This study analyzes 156 genomes of Toxoplasma gondii and provides estimates of the parasite's mutation rate and generation time. It reveals that a specific haplotype is associated with the spread of the parasite through cats, indicating its role in sexual reproduction.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rajib Acharjee, Keith K. Talaam, Endah D. Hartuti, Yuichi Matsuo, Takaya Sakura, Bundutidi M. Gloria, Shinya Hidano, Yasutoshi Kido, Mihoko Mori, Kazuro Shiomi, Masakazu Sekijima, Tomoyoshi Nozaki, Kousuke Umeda, Yoshifumi Nishikawa, Shinjiro Hamano, Kiyoshi Kita, Daniel K. Inaoka
Summary: Toxoplasma gondii is a protozoan parasite that infects a large portion of the global human population. A new potential drug target, TgMQO, has been identified in this study, and a novel expression system was developed to study its characteristics. Ferulenol, an MQO inhibitor, showed promising inhibitory effects on TgMQO, with distinct binding sites from other known inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Caroline Gubser Keller, Youngah Shin, Alex Mas Monteys, Nicole Renaud, Martin Beibel, Natalia Teider, Thomas Peters, Thomas Faller, Sophie St-Cyr, Judith Knehr, Guglielmo Roma, Alejandro Reyes, Marc Hild, Dmitriy Lukashev, Diethilde Theil, Natalie Dales, Jang-Ho Cha, Beth Borowsky, Ricardo Dolmetsch, Beverly L. Davidson, Rajeev Sivasankaran
Summary: Huntington's Disease is a neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. The orally available and brain penetrant small molecule branaplam lowers HTT transcript by promoting inclusion of a poison exon or pseudoexon.
NATURE COMMUNICATIONS
(2022)
Article
Veterinary Sciences
Ningbo Xia, Nuo Ji, Longjiao Li, Yuan Huang, Congshan Yang, Xuefang Guo, Qinghong Guo, Bang Shen, Lihua Xiao, Yaoyu Feng
Summary: This study investigated the seroprevalence and risk factors of T. gondii infection in cats across China. The study found higher infection rates in Sichuan, Chongqing, and Hunan, and reported the seroprevalence in Qinghai, Anhui, Jiangxi, Shaanxi, and Ningxia for the first time. Age and lifestyle (stray or pet) of cats were identified as risk factors for T. gondii infection.
BMC VETERINARY RESEARCH
(2022)
Review
Infectious Diseases
Tahereh Mikaeili Galeh, Shahabeddin Sarvi, Seyed Abdollah Hosseini, Ahmad Daryani
Summary: Toxoplasmosis, caused by Toxoplasma gondii, is a common food-borne infection in humans. In rodent populations, atypical genotypes are dominant, while clonal strains circulate with low genetic diversity in this mammal species.
TRANSBOUNDARY AND EMERGING DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Yazhen Ma, Xinru Cao, Hui Wang, Xingju Song, Dandan Hu
Summary: Tilmicosin and acetylisovaleryltylosin tartrate (ATLL) have potent anti-Toxoplasma activities, inhibiting the growth and proliferation of the parasite. ATLL shows strong inhibitory effects on intracellular parasites, while tilmicosin suppresses extracellular parasites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Microbiology
Samantha A. Michaels, Matthew A. Hulverson, Grant R. Whitman, Linh T. Tran, Ryan Choi, Erkang Fan, Case W. McNamara, Melissa S. Love, Kayode K. Ojo
Summary: A phenotypic screen of the ReFRAME compound library identified Mavelertinib as a potential therapeutic for giardiasis. It showed efficacy against metronidazole-resistant strains and demonstrated good results in a mouse model.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(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
Chemistry, Medicinal
Tswene D. Seanego, Hlamulo E. Chavalala, Hendrik H. Henning, Charles B. de Koning, Heinrich C. Hoppe, Kayode K. Ojo, Amanda L. Rousseau
Summary: A series of pyrrolo[2,3-d]pyrimidines were designed and evaluated in vitro for their inhibitory activity against PfCDPK4 and PfCDPK1. Four compounds exhibited promising inhibitory activity.
Article
Biochemistry & Molecular Biology
Carrie S. Tambo, Sarvind Tripathi, B. Gayani K. Perera, Dustin J. Maly, Alexander J. Bridges, Gert Kiss, Seth M. Rubin
Summary: Cyclin-dependent kinases (CDKs) are crucial regulators of cell proliferation and have been studied as potential targets for cancer therapy. The interaction between CDKs and cyclins, their activators, plays a central role in cell cycle progression. In this study, a biolayer interferometry assay was used to quantify CDK-cyclin binding interactions. The results showed that Type I inhibitors increase the affinity between CDK2 and cyclin A by slowing down cyclin dissociation, while Type II inhibitors and other small-molecule CDK2 binders have different effects on cyclin association and dissociation kinetics, leading to decreased affinity. The findings suggest that the plasticity of the CDK2 active site contributes to the differential impact of small molecules on cyclin binding kinetics.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tim Aguirre, Ellen Teichmann, Florian Q. Roempp, Ruthey Vivier, Cole Bryant, Matthew A. Hulverson, Wesley C. Van Voorhis, Kayode K. Ojo, J. Stone Doggett, Dorothea Fiedler, Stefan Hecht
Summary: This study developed photoswitchable azopyrazoles as inhibitors to selectively target CDPK1 from Toxoplasma gondii. The inhibitory activity of CDPK1 is dependent on the size of the gatekeeper residue. The photoswitchable inhibitors also showed activity against T. gondii and Cryptosporidium parvum infections in a cell culture model.
ACS CHEMICAL BIOLOGY
(2023)
Article
Microbiology
Matthew A. Hulverson, Ryan Choi, Deborah A. Schaefer, Dana P. Betzer, Molly C. McCloskey, Grant R. Whitman, Wenlin Huang, Sangun Lee, Andy Pranata, Malcolm D. McLeod, Kennan C. Marsh, Dale J. Kempf, Bruce E. LeRoy, Mark T. Zafiratos, Aimee L. Bielinski, Robert C. Hackman, Kayode K. Ojo, Samuel L. M. Arnold, Lynn K. Barrett, Saul Tzipori, Michael W. Riggs, Erkang Fan, Wesley C. Van Voorhis
Summary: Recent advances in the development of bumped kinase inhibitors for treating cryptosporidiosis have focused on a specific structure known as 5-aminopyrazole-4-carboxamide scaffold, which has shown superior efficacy, reduced hERG inhibition, and excellent safety profiles in vitro. Three compounds (BKI-1770, -1841, and -1708) demonstrated strong effectiveness in mice infected with C. parvum. While BKI-1770 and BKI-1841 were effective in a C. parvum calf model, they caused limb hyperflexion. Toxicity experiments in rats and calves revealed bone toxicity at slightly higher doses than the efficacious dose for BKI-1770. Both BKI-1770 and BKI-1841 showed neurological effects in mice, and BKI-1770 also displayed bone toxicity. However, BKI-1708 showed no signs of bone toxicity or neurological effects in mice, making it a promising candidate for further evaluation.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Plant Sciences
Jin Woo Lee, Jennifer E. E. Collins, Matthew A. A. Hulverson, Laarni Kendra T. Aguila, Caroline M. M. Kim, Karen L. L. Wendt, Debopam Chakrabarti, Kayode K. K. Ojo, Gwendolyn E. E. Wood, Wesley C. C. Van Voorhis, Robert H. H. Cichewicz
Summary: Xanthoquinodins are a unique class of compounds found in several fungal species, and they have been reported as secondary metabolites. A fungal extract from Trichocladium sp. was found to have strong inhibitory effects against several human pathogens. Six new compounds and several previously reported natural products were identified through purification and analysis. Among them, Xanthoquinodins A1 and A2 showed the most promising broad-spectrum inhibitory effects against multiple human pathogens.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Cindy T. T. Wei, Nicholas A. A. Popp, Omri Peleg, Rachel L. L. Powell, Elhanan Borenstein, Dustin J. J. Maly, Douglas M. M. Fowler
Summary: Researchers have developed a chemically activated DNA-binding Cas9 switch called ciCas9, which enables temporal control over seven Cas9 effectors including base editors and transcriptional activators. Using this switch, they analyzed the kinetics of base editing and found that editing occurs within hours and early rapid editing predicts the final editing magnitude. They also discovered that editing at preferred nucleotides increases bystander edits. The ciCas9 switch offers a versatile approach for generating chemically controlled Cas9 effectors and enables precise temporal effector control for kinetic studies.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Virology
Anise N. N. Happi, Akeemat O. O. Ayinla, Olusola A. A. Ogunsanya, Ayotunde E. E. Sijuwola, Femi M. M. Saibu, Kazeem Akano, Uwem E. E. George, Adebayo E. E. Sopeju, Peter M. M. Rabinowitz, Kayode K. K. Ojo, Lynn K. K. Barrett, Wesley C. C. Van Voorhis, Christian T. T. Happi
Summary: This study investigated the presence of SARS-CoV-2 in various animals in Nigeria and found that the virus can infect multiple animal species, including poultry, pigs, domestic ruminants, and lizards. This highlights the ability of SARS-CoV-2 to spread among animals and emphasizes the importance of continuous monitoring and intervention.
Article
Microbiology
Matthew A. Hulverson, Samantha A. Michaels, Jin Woo Lee, Karen L. Wendt, Linh T. Tran, Ryan Choi, Wesley C. Van Voorhis, Robert H. Cichewicz, Kayode K. Ojo
Summary: In this study, natural products and fungal extracts were screened for their ability to inhibit the growth of Giardia lamblia, leading to the discovery of novel chemical scaffolds that can potentially be developed into effective antigiardial agents.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Michael K. Fenwick, Alexandra R. Reers, Yi Liu, Rachael Zigweid, Banumathi Sankaran, Janis Shin, Matthew A. Hulverson, Bradley Hammerson, Elena Fernandez Alvaro, Peter J. Myler, Alexis Kaushansky, Wesley C. Van Voorhis, Erkang Fan, Bart L. Staker
Summary: Two potential hit compounds were identified that could be effective against Cryptosporidium, and their interaction with CpNMT was validated, providing insights for identifying drug targets for treating protozoan parasite infections.
ACS INFECTIOUS DISEASES
(2023)
