Article
Chemistry, Medicinal
Preeti Singh, Chiranjeev Sharma, Bhawana Sharma, Anupam Mishra, Drishti Agarwal, Deepika Kannan, Jana Held, Shailja Singh, Satish K. Awasthi
Summary: This study reports a rapid method for synthesizing N-sulfonylpiperidine dispiro-1,2,4,5-tetraoxane analogs for antimalarial research. The synthesized compounds were characterized and evaluated for their in vitro and in vivo antimalarial activities.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Yvette S. Levray, Bianca Bana, Sarah J. Tarr, Emilia J. McLaughlin, Peter Rossi-Smith, Anita Waltho, Georgina H. Charlton, Riccardo Zenezini Chiozzi, Colin R. Straton, Konstantinos Thalassinos, Andrew R. Osborne
Summary: During malaria infection, the malaria parasite exports proteins into human red blood cells. Some of these proteins become embedded in membranes and are referred to as membrane proteins. The mechanism of how these membrane proteins are transported is poorly understood. This study reveals that a subset of membrane proteins enter into the lumen of the endoplasmic reticulum and may represent a unique drug target.
Article
Microbiology
Julie-Anne Gabelich, Josephine Gruetzke, Florian Kirscht, Oliver Popp, Joachim M. Matz, Gunnar Dittmar, Melanie Rug, Alyssa Ingmundson
Summary: This study aimed to find and characterize protein components of the intraerythrocytic Plasmodium-induced membrane structures (IBIS), and found that these proteins play important roles in the infected stage of the parasite.
Article
Biology
Michal Pasternak, Julie M. J. Verhoef, Wilson Wong, Tony Triglia, Michael J. Mlodzianoski, Niall Geoghegan, Cindy Evelyn, Ahmad Z. Wardak, Kelly Rogers, Alan F. Cowmarc
Summary: The RhopH complex is not formed during merozoite invasion. Clag3 is released directly into the host cell cytoplasm, while RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of the Clag3/RhopH2/RhopH3 complex and its incorporation into the host cell membrane concomitant with activation of nutrient uptake.
COMMUNICATIONS BIOLOGY
(2022)
Article
Microbiology
Tsubasa Nishi, Izumi Kaneko, Shiroh Iwanaga, Masao Yuda
Summary: This study reveals the crucial role of transcriptional activity in Plasmodium zygotes, especially the function of a novel transcription factor AP2-Z, in promoting ookinete development. The findings suggest the existence of a transcription factor cascade and provide potential target genes for understanding Plasmodium zygote/ookinete development and developing transmission blocking vaccines.
Article
Infectious Diseases
Hong Fei, Muhammad Ali-ul-Husnain Naqvi, Sana Zahra Naqvi, Lixin Xu, Xiaokai Song, Xiangrui Li, Ruofeng Yan
Summary: The study cloned the GILT from Trichinella spiralis and confirmed its key role in antigen processing and presentation. Knocking down the expression of Tsp-GILT using siRNA revealed that GILT may play an important role in the development of T. spiralis parasite.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Parasitology
Forough Momenfam, Mehdi Nateghpour, Afsaneh Motevalli Haghi, Leila Farivar, Mehdi Mohebali, Homa Hajjaran, Soudabeh Etemadi
Summary: The study found that the combination of chitosan and chloroquine has a stronger inhibitory effect on Plasmodium berghei and P. falciparum, significantly extending the survival time of the infected mice.
IRANIAN JOURNAL OF PARASITOLOGY
(2021)
Article
Cell Biology
Adithya Dhamodharan, Hajime Okada, Masafumi Muraoka, Danelle Wright, Akemi Okubo, Yumiko Saga
Summary: Using the AID method, we successfully studied the impact of DDX6 on P-body assembly and cellular status, and observed changes in the transcriptome.
DEVELOPMENT GROWTH & DIFFERENTIATION
(2022)
Review
Chemistry, Medicinal
Agnieszka Zagorska, Anna Jaromin
Summary: Malaria, caused by Plasmodium parasites transmitted by infected mosquitoes, is still a major threat in tropical regions. The growing resistance of the parasites to antimalarial drugs has led to the search for new molecules that can target specific proteins in the parasite. One promising target is PfATP4, a protein involved in ion transport, which is exclusive to the parasite and can be inhibited to kill the parasite. This review discusses the function of PfATP4 and the development of inhibitors that show promising results in preclinical and clinical studies.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Parasitology
Nanang R. Ariefta, Aiko Kume, Yoshifumi Nishikawa, Tomoyo Taniguchi, Rika Umemiya-Shirafuji, Shunji Kasai, Hiroshi Suzuki
Summary: The study demonstrated that alpha-TEA is effective against both murine and human malaria in vivo and in vitro. Administration of 1.5% alpha-TEA for 14 days post-infection resulted in 88% survival rate in infected mice during the experimental period.
ACTA PARASITOLOGICA
(2022)
Article
Microbiology
Mikha Gabriela, Kathryn M. Matthews, Cas Boshoven, Betty Kouskousis, Thorey K. Jonsdottir, Hayley E. Bullen, Joyanta Modak, David L. Steer, Brad E. Sleebs, Brendan S. Crabb, Tania F. de Koning-Ward, Paul R. Gilson
Summary: The malaria parasite Plasmodium falciparum exports a large number of proteins into host erythrocytes, modifying the physiology of the host cells. This study has identified a subcomplex consisting of EXP2 and PTEX150 that facilitates the docking of HSP101. It has also demonstrated that HSP101 can interact with specific cargo proteins in the parasite's ER and guide them to the parasitophorous vacuole membrane. These findings provide insights into the mechanism of how exported proteins are targeted to PTEX.
Review
Immunology
Rebecca C. S. Edgar, Natalie A. Counihan, Sheena McGowan, Tania F. de Koning-Ward
Summary: Plasmodium falciparum malaria remains a global health problem due to the parasite's resistance to all antimalarials. Current therapeutics target the parasite's digestive vacuole, and studying this organelle is essential for understanding its function and developing new treatments.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Adam J. Blanch, Juan Nunez-Iglesias, Arman Namvar, Sebastien Menant, Oliver Looker, Vijay Rajagopal, Wai-Hong Tham, Leann Tilley, Matthew W. A. Dixon
Summary: The study demonstrates that as reticulocytes mature into RBCs, there is a decrease in cell surface area and an increase in the density of the spectrin-actin network, along with slight increases in inter-junctional distance and junctional density. Additionally, the edge region of mature RBCs contains more junctional complexes compared to the dimple region, supported by a 2% increase in band 4.1 density.
JOURNAL OF STRUCTURAL BIOLOGY-X
(2022)
Article
Microbiology
Yawei Du, Carlo Giannangelo, Wei He, Gerald J. Shami, Wenya Zhou, Tuo Yang, Darren J. Creek, Con Dogovski, Xinsong Li, Leann Tilley
Summary: This study introduces a liposome-like prodrug as a treatment for artemisinin-resistant malaria. The results show that this multilamellar liposome-like assembly can sustainably release the drug and enhance the efficacy against resistant parasites in vitro. Analysis of parasite proteostasis pathways reveals the mechanism of action of this liposome-like assembly.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Hayley E. Bullen, Paul R. Sanders, Madeline G. Dans, Thorey K. Jonsdottir, David T. Riglar, Oliver Looker, Catherine S. Palmer, Betty Kouskousis, Sarah C. Charnaud, Tony Triglia, Mikha Gabriela, Molly Parkyn Schneider, Jo-Anne Chan, Tania F. de Koning-Ward, Jake Baum, James W. Kazura, James G. Beeson, Alan F. Cowman, Paul R. Gilson, Brendan S. Crabb
Summary: Infection with Plasmodium falciparum parasites leads to a significant number of deaths each year. Understanding the proteins involved in parasite invasion and growth within human erythrocytes is important for developing new therapeutic strategies. One of these proteins, P113, has been found to play a role in both invasion and intracellular processes. Through our investigation, we discovered that P113 interacts with the protein export machinery and various proteins associated with the parasite vacuole. Furthermore, disrupting P113 affects the architecture of the vacuole membrane. This research provides insights into the function of P113 and its potential as a target for malaria treatment.
MOLECULAR MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Stanley C. Xie, Riley D. Metcalfe, Elyse Dunn, Craig J. Morton, Shih-Chung Huang, Tanya Puhalovich, Yawei Du, Sergio Wittlin, Shuai Nie, Madeline R. Luth, Liting Ma, Mi-Sook Kim, Charisse Flerida A. Pasaje, Krittikorn Kumpornsin, Carlo Giannangelo, Fiona J. Houghton, Alisje Churchyard, Mufuliat T. Famodimu, Daniel C. Barry, David L. Gillett, Sumanta Dey, Clara C. Kosasih, William Newman, Jacquin C. Niles, Marcus C. S. Lee, Jake Baum, Sabine Ottilie, Elizabeth A. Winzeler, Darren J. Creek, Nicholas Williamson, Michael W. Parker, Stephen Brand, Steven P. Langston, Lawrence R. Dick, Michael D. W. Griffin, Alexandra E. Gould, Leann Tilley
Summary: This study identifies aminoacyl transfer RNA synthetases as potential drug targets and presents a novel compound that can inhibit these enzymes, effectively killing the malaria parasite.
Review
Microbiology
Natalie A. Counihan, Hope C. Chernih, Tania F. de Koning-Ward
Summary: Post-translational modifications play a crucial role in regulating cellular processes in eukaryotic proteins, and lipidation is particularly important in Plasmodium parasites. This review discusses lipid modification processes and their potential as drug targets for malaria.
CURRENT OPINION IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jiahong Li, Gerald J. Shami, Ellie Cho, Boyin Liu, Eric Hanssen, Matthew W. A. Dixon, Leann Tilley
Summary: This study investigates the organization and orientation of microtubules in the sexual stage gametocytes of Plasmodium falciparum, the malaria parasite. It shows that a non-mitotic microtubule organizing center is involved in the assembly of cytoplasmic and nuclear microtubules, and plays a central role in chromatin organization, inner membrane complex positioning, and subpellicular microtubule formation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Rebecca C. S. Edgar, Ghizal Siddiqui, Katheryn Hjerrild, Tess R. Malcolm, Natalie B. Vinh, Chaille T. Webb, Clare Holmes, Christopher A. MacRaild, Hope C. Chernih, Willy W. Suen, Natalie A. Counihan, Darren J. Creek, Peter J. Scammells, Sheena McGowan, Tania F. de Koning-Ward
Summary: The study demonstrates the importance of leucine aminopeptidase PfA-M17 for the survival of Plasmodium falciparum, providing parasites with essential amino acids for growth. Loss of PfA-M17 results in parasites exhibiting multiple digestive vacuoles at the trophozoite stage.
Article
Immunology
Tabinda Hussain, Angela Nguyen, Carmel Daunt, Daniel Thiele, Ee Shan Pang, Jasmine Li, Aidil Zaini, Meredith O'Keeffe, Colby Zaph, Nicola L. Harris, Kylie M. Quinn, Nicole L. La Gruta
Summary: CD8 virtual memory T (TVM) cells, which have undergone partial differentiation in response to cytokines, can increase after helminth infection, leading to improved pathogen clearance in young mice. However, as mice age, TVM cells lose their proliferative capacity and show signs of senescence. In this study, the researchers found that the increase in TVM cells after helminth infection is driven by proliferation of existing TVM cells, rather than differentiation of true naive CD8 T cells. Additionally, TVM cells have the highest proliferation rate compared to other CD8 T cells in response to helminth infection and IL-15. Furthermore, TVM cells from aged mice do not undergo expansion after helminth infection due to intrinsic and extrinsic changes associated with aging.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Parasitology
Sarah A. Knowler, Anya Shindler, Jennifer L. Wood, Asha Lakkavaram, Colleen J. Thomas, Tania F. de Koning-Ward, Elisa L. Hill-Yardin, Teresa G. Carvalho, Ashley E. Franks
Summary: Cerebral malaria is the most severe form of malaria and can have long-term neurological consequences. Research has shown the importance of the gut microbiome in brain health, but little is known about its role in malaria. In this study, mice infected with Plasmodium berghei ANKA parasites showed significant differences in bacterial communities compared to non-infected mice. The findings suggest that the gut microbiome is affected by the infection and could be a target for intervention strategies to reduce the severity of cerebral malaria.
PARASITOLOGY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Katherine R. Balka, Rajan Venkatraman, Tahnee L. Saunders, Angus Shoppee, Ee Shan Pang, Zoe Magill, Jihane Homman-Ludiye, Cheng Huang, Rachael M. Lane, Harrison M. York, Peck Tan, Ralf B. Schittenhelm, Senthil Arumugam, Benjamin T. Kile, Meredith O'Keeffe, Dominic De Nardo
Summary: cGAS-STING signalling is initiated by detecting foreign or mislocalised DNA within the cytosol, leading to the production of interferons and inflammatory cytokines. STING is degraded within lysosomes, but the mechanisms controlling its delivery are poorly understood. In this study, the researchers used proteomics and microscopy to identify that the ESCRT pathway detects ubiquitinated STING on vesicles, facilitating its degradation in macrophages. Disruption of the ESCRT pathway enhances STING signalling and cytokine production, revealing a mechanism for effective termination of the pathway.
Article
Microbiology
Emma McHugh, Michaela S. Bulloch, Steven Batinovic, Cameron J. Patrick, Drishti K. Sarna, Stuart A. Ralph
Summary: The proteins responsible for destroying nonsense transcripts in the malaria parasite were found to have no impact on the abundance of these transcripts. Additionally, efficient CRISPR-Cas9 editing of the malaria parasite was demonstrated using commercial Cas9 nuclease and synthetic guide RNA, making genomic modifications easier in this genetically intractable organism.
Article
Biochemistry & Molecular Biology
Saeed Maymand, Asha L. Lakkavaram, Wasan Naser, Parisa Rasighaemi, Daniel Dlugolenski, Clifford Liongue, John Stambas, Tania F. de Koning-Ward, Alister C. Ward
Summary: This study reveals the regulatory role of CISH in both basal and EPO-induced erythropoiesis in vivo.
Meeting Abstract
Infectious Diseases
Winfrey Hoo, Jennifer Payne, Julien Tailhades, Jemma Gullick, Rachel Cass, Ee Shan Pang, Meredith O'Keeffe, Felix Ellett, Alex Fulcher, Daniel Irima, Anton Peleg, Max Cryle
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)