Review
Microbiology
Ming Pan, Ceng-Ceng Ge, Yi-Min Fan, Qi-Wang Jin, Bang Shen, Si-Yang Huang
Summary: This article reviews recent advances in the study of bradyzoite biology and stage conversion of Toxoplasma gondii, aiming to highlight the determinants associated with bradyzoite development and provide insights for better strategies on controlling toxoplasmosis.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biology
Nicholas Rinkenberger, Michael E. Abrams, Sumit K. Matta, John W. Schoggins, Neal M. Alto, L. David Sibley
Summary: The study investigated the role of IFN gamma-induced ISGs in restricting Toxoplasma gondii infection, and identified RARRES3 as a novel factor restricting parasite infection. The limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFN gamma-mediated immunity to T. gondii infection is a complex, multifactorial process.
Article
Microbiology
Anatoli V. Naumov, Chengqi Wang, Dale Chaput, Li-Min Ting, Carmelo A. Alvarez, Thomas Keller, Ahmed Ramadan, Michael W. White, Kami Kim, Elena S. Suvorova
Summary: In this study, the central machinery of the T. gondii restriction checkpoint was identified, consisting of TgCrk2 kinase and three atypical T. gondii cyclins. The study revealed the independent roles of TgCycP1, TgCycP2, and TgCyc5 in parasite growth and development.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Marc-Jan Gubbels, David J. P. Ferguson, Sudeshna Saha, Julia D. Romano, Suyog Chavan, Vincent A. Primo, Cynthia Michaud, Isabelle Coppens, Klemens Engelberg
Summary: Apicomplexa is famous for its apical complex at the top, while the basal complex at the other end has been overshadowed. However, in the past decade, a variety of functions have been associated with the basal complex, and progress has been made in understanding its structure.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Fuqiang Fan, Lilan Xue, Xiaoyan Yin, Nishith Gupta, Bang Shen
Summary: Transition from asexual to sexual development in Toxoplasma gondii is controlled by a novel transcription factor, TgAP2XII-1. This factor represses the presexual development in the asexual tachyzoite stage. Parasites lacking AP2XII-1 exhibit a merozoite-type transcriptional profile. This study provides insight into the sexual commitment of T. gondii and suggests a potential method for culturing presexual stages.
Article
Immunology
Ahlam Elmasry, Wafaa A. Aboukamar, Heba Hany, Manar S. Elmehankar
Summary: The study found that Roflumilast has a potential effect on the tachyzoite-bradyzoite transition in toxoplasmosis. The group treated earlier with 10 mg/kg of Roflumilast showed the best results, significantly reducing T. gondii cyst count, size, and IL-12 level.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Congcong Lyu, Xuke Yang, Jichao Yang, Lun Hou, Yanqin Zhou, Junlong Zhao, Bang Shen
Summary: This study identified a starch synthase required for amylopectin synthesis in Toxoplasma gondii, which plays a critical role in parasite growth, development, and virulence. Disrupting this enzyme may impact the pathogen's proliferation and ability to move between different life cycle stages, highlighting a potential drawback in using such mutants as vaccine candidates.
Article
Microbiology
Yun Chen, Qi Liu, Jun-Xin Xue, Man-Yu Zhang, Xiao-Ling Geng, Quan Wang, Wei Jiang
Summary: Toxoplasma gondii, a widespread apicomplexan parasite, possesses an important antioxidant system to defend against host-induced oxidative stress. CRISPR/Cas9 screening identified genes like HP1 that are critical for managing oxidative stress and may contribute to T. gondii virulence in mice.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Hironori Bando, Yasuhiro Fukuda, Nina Watanabe, Jeje Temitope Olawale, Kentaro Kato
Summary: This study reveals that abnormal glutamine metabolism induced by both interferon-gamma stimulation and Toxoplasma gondii infection triggers cyst formation in human neuroblastoma cells. The findings suggest that glutamine starvation in host cells is an important trigger of T. gondii stage conversion in human neurons.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Microbiology
Kourosh Zarringhalam, Sida Ye, Jingjing Lou, Yasaman Rezvani, Marc-Jan Gubbels
Summary: The cell division cycle of T. gondii is regulated by AP2 transcription factors, which drive gene expression and the progression of the lytic cycle. Major changes in gene expression occur during the transition from the cell cycle to the extracellular state or differentiation into bradyzoites, and this transition leads to the expression of a shared set of AP2 transcription factors, indicating a potential shared stress response.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jichao Yang, Xuke Yang, Anqi Liu, Yaqiong Li, Zhipeng Niu, Congcong Lyu, Xiaohan Liang, Ningbo Xia, Jianmin Cui, Mingjun Li, Ping Wu, Chao Peng, Bang Shen
Summary: The study revealed that AMPK plays crucial roles in controlling cell cycle progression and bradyzoite development in Toxoplasma. Deletion of the beta subunit of AMPK resulted in DNA damage and increased conversion to bradyzoites. Under alkaline stress, AMPK beta mutants transitioned to a bradyzoite-like state but with impaired cell division pattern and compromised parasite viability.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Microbiology
Sophie Zhu, Elizabeth Van Wormer, Beatriz Martinez-Lopez, Lilian Maria Garcia Bahia-Oliveira, Renato Augusto DaMatta, Pedro Souto Rodrigues, Karen Shapiro
Summary: This study used Bayesian quantitative risk assessment to estimate the relative attribution of two primary parasite stages (bradyzoite and oocyst) in food-related toxoplasmosis in Brazil. The results showed that oocyst contamination in fruits and greens contributed more to the infection risk compared to bradyzoite contamination in meats. Due to the lack of regional food contamination prevalence data and uncertainty in model parameters, this study provides a preliminary estimate of the relative importance of food products in toxoplasmosis and identifies important knowledge gaps for future research and policy actions.
Article
Microbiology
Wei Li, Janessa Grech, Johannes Felix Stortz, Matthew Gow, Javier Periz, Markus Meissner, Elena Jimenez-Ruiz
Summary: Using a conditional Cas9-system, a phenotypic screen identified two genes in Toxoplasma gondii that play different roles in host cell egress. This method helps overcome the difficulty of assigning gene functions in apicomplexan parasites and has potential for identifying more related genes in future studies.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Erica S. Martins-Duarte, Juliana de Araujo Portes, Ramon Borges da Silva, Hugo Silva Pires, Simon J. Garden, Wanderley de Souza
Summary: Toxoplasma gondii is a common parasitic disease worldwide, with limited therapy options. Chemical modification of 1,10-phenanthroline to new derivatives has significantly improved anti-T. gondii activity, potentially serving as lead compounds for the treatment of acute and chronic phases of toxoplasmosis.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Celine Dard, Baptiste Leforestier, Flaviane Francisco Hilario, Mohamed Dit Mady Traore, Marie-Ange Lespinasse, Basile Peres, Marie-Carmen Molina, Rossimiriam Pereira de Freitas, Anne Milet, Daniele Maubon, Yung-Sing Wong
Summary: FR235222 is a natural tetra-cyclopeptide that inhibits histone deacetylases and is effective on mammalian cells and intracellular apicomplexan parasites. It is characterized by a zinc-binding group for binding to histone deacetylases and a cyclic tetrapeptide moiety crucial for cell permeability. The molecule has shown promise for cell penetration and inhibition of histone deacetylases, even in parasite cells.
Article
Chemistry, Multidisciplinary
James R. D. Montgomery, Karl Kempf, Daniel M. Miles-Barrett, Oxana Kempf, Tomas Lebl, Nicholas J. Westwood
Article
Biology
Alex Hunt, Matthew Robert Geoffrey Russell, Jeanette Wagener, Robyn Kent, Romain Carmeille, Christopher J. Peddie, Lucy Collinson, Aoife Heaslip, Gary E. Ward, Moritz Treeck
Article
Chemistry, Multidisciplinary
Ganyuan Xiao, James R. D. Montgomery, Christopher S. Lancefield, Isabella Panovic, Nicholas J. Westwood
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Agricultural Engineering
Flora Foltanyi, Julie E. Hawkins, Isabella Panovic, Eve J. Bird, Tracey M. Gloster, Christopher S. Lancefield, Nicholas J. Westwood
BIOMASS & BIOENERGY
(2020)
Review
Microbiology
Carla E. Lanze, Rafael M. Gandra, Jenna E. Foderaro, Kara A. Swenson, Lois M. Douglas, James B. Konopka
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2020)
Article
Microbiology
Pramod K. Rompikuntal, Robyn S. Kent, Ian T. Foe, Bin Deng, Matthew Bogyo, Gary E. Ward
Summary: The key binding element between TgMLC1 and TgGAP45 in the force transduction machinery of T. gondii was found to be the palmitoylation of C8 and C11 residues on TgMLC1, contradicting the current model. Surprisingly, mutations disrupting this binding had little impact on parasite motility, challenging the widely held linear motor model and emphasizing the need for further research on how apicomplexan parasites generate necessary forces for movement.
Article
Chemistry, Multidisciplinary
Laura Elena Hofmann, Lisa-Marie Altmann, Oliver Fischer, Lea Prusko, Ganyuan Xiao, Nicholas J. Westwood, Markus R. Heinrich
Summary: A novel two-step reaction sequence was reported in this study, which converts organosolv lignin into phenols through oxidation with DDQ and nitrogen monoxide followed by cleavage with hydrazine and potassium hydroxide. The resulting phenols do not bear any substituent at the 4-position.
Article
Biochemistry & Molecular Biology
Ganyuan Xiao, Magnus S. Alphey, Fanny Tran, Lisa Pirrie, Pierre Milbeo, Yi Zhou, Jasmine K. Bickel, Oxana Kempf, Karl Kempf, James H. Naismith, Nicholas J. Westwood
Summary: The study focused on exploring the allosteric site of RmlA, leading to the discovery of potent inhibitors that could be improved by modifying the C6-NH2 of the pyrimidinedione core structure. X-ray crystallographic analysis of the complexes of P. aeruginosa RmlA with the novel analogues revealed how C6-aminoalkyl substituents can be used to position a modifiable amine just outside the allosteric pocket.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Ganyuan Xiao, Gerard Su, Alexandra M. Z. Slawin, Nicholas Westwood
Summary: Members of the karrikin family are known to promote plant germination after fires. This report describes the synthesis of these compounds from a biomass-derived product stream, obtained during the fractionation of biomass for high quality lignins.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Craig A. Johnston, David B. Cordes, Tomas Lebl, Alexandra M. Z. Slawin, Nicholas J. Westwood
Summary: The study investigates the synthetic route of the bioactive natural product perophoramidine and an alternative N-chlorosuccinimde-mediated reaction for its core structure. Unexpected rearrangement of the core structure was observed during attempts to synthesize the natural product, with X-ray crystallographic analysis providing important analytical confirmation for the assigned structures.
Article
Biology
Rachel Stadler, Shane R. Nelson, David M. Warshaw, Gary E. Ward
Summary: Toxoplasma gondii is a protozoan parasite that infects a significant portion of the world's population, using a unique form of substrate-dependent motility to invade host cells and disseminate throughout the body. Recent research shows that the predominant forces exerted by the moving parasite are periodic and directed inward, leading to a visible constriction in the parasite's plasma membrane. This suggests a closer connection between parasite motility and host cell invasion than previously recognized.
Article
Biochemistry & Molecular Biology
Anne Kelsen, Robyn J. Kent, Anne V. Snyder, Eddie Wehri, Stephen Bishop, Rachel K. Stadler, Cameron J. Powell, Bruno Martorelli M. di Genova, Pramod J. Rompikuntal, Martin Boulanger, David E. Warshaw, Nicholas Westwood, Julia Schaletzky, Gary Ward
Summary: In this study, a drug called KNX-002 was found to effectively inhibit the motility and growth of Toxoplasma gondii, and slow down disease progression in mice. The research confirmed that a parasite-specific myosin protein, TgMyoA, is a target for KNX-002, providing a promising approach to treat diseases caused by T. gondii and other apicomplexan parasites.
Article
Chemistry, Multidisciplinary
Daniel J. Davidson, Fei Lu, Laura Faas, Daniel M. Dawson, Geoffrey P. Warren, Isabella Panovic, James R. D. Montgomery, Xiaoyan Ma, Boris G. Bosilkov, Alexandra M. Z. Slawin, Tomas Lebl, Afroditi Chatzifragkou, Steve Robinson, Sharon E. Ashbrook, Liz J. Shaw, Smilja Lambert, Isabella Van Damme, Leonardo D. Gomez, Dimitris Charalampopoulos, Nicholas J. Westwood
Summary: Cocoa pod husks, an underutilized resource in chocolate manufacturing, contain lignin with potential applications. An optimized extraction method led to high-quality lignin, allowing for further investigation of its structure and chemical transformation abilities. Preliminary analysis of other product streams from the husks was also conducted.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Green & Sustainable Science & Technology
Fiorella Picchioni, Geoffrey P. Warren, Smilja Lambert, Kelvin Balcombe, J. Steve Robinson, Chittur Srinivasan, Leonardo D. Gomez, Laura Faas, Nicholas J. Westwood, Afroditi Chatzifragkou, Dimitris Charalampopoulos, Liz J. Shaw
Article
Chemistry, Multidisciplinary
Haiwei Guo, Daniel M. Miles-Barrett, Bo Zhang, Aiqin Wang, Tao Zhang, Nicholas J. Westwood, Changzhi Li