Article
Biotechnology & Applied Microbiology
Jack Adderley, Christian Doerig
Summary: This study fills gaps in the kinomes of Plasmodium falciparum and Plasmodium vivax, highlighting their similarities and differences for target selection. It also identifies kinases that are not suitable targets for drug discovery due to their high similarity with human counterparts.
Article
Immunology
Nan Hou, Shanshan Li, Ning Jiang, Xianyu Piao, Yu Ma, Shuai Liu, Qijun Chen
Summary: The study uncovered the developmental transcriptome of asexual parasites of P. falciparum and identified a group of previously unknown merozoite proteins that may play crucial roles in the invasion process of merozoites.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Gunjan Arora, Andaleeb Sajid, Yu-Min Chuang, Yuemei Dong, Akash Gupta, Kristen Gambardella, Kathleen DePonte, Lionel Almeras, George Dimopolous, Erol Fikrig
Summary: Malaria is a vector-borne disease caused by Plasmodium sporozoites, and mosquito saliva proteins can influence pathogen transmission and early infection. Anopheles gambiae Sporozoite-Associated Protein (AgSAP) interacts directly with Plasmodium sporozoites, inhibits inflammatory responses, and plays a role in early infection modulation. Individuals in endemic malaria regions generate antibodies against AgSAP, suggesting its potential as a biomarker for disease prevalence and epidemiological analysis.
Article
Medicine, General & Internal
Sinmanus Vimonpatranon, Sittiruk Roytrakul, Narumon Phaonakrop, Kittima Lekmanee, Anyapat Atipimonpat, Narinee Srimark, Kasama Sukapirom, Kesinee Chotivanich, Ladawan Khowawisetsut, Kovit Pattanapanyasat
Summary: In infectious diseases, EVs released from pathogen-infected cells can regulate immune responses and carry specific human proteins, while most pathogen proteins in the EVs are common across different types. Pf-MVs were found to attenuate parasite invasion efficiency, with a greater effect in culture-adapted isolates. This suggests that Pf-EVs play a role in quorum sensing and regulation of parasite growth-density.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biology
Abdirahman Abdi, Fiona Achcar, Lauriane Sollelis, Joao Luiz Silva-Filho, Kioko Mwikali, Michelle Muthui, Shaban Mwangi, Hannah W. Kimingi, Benedict Orindi, Cheryl Andisi Kivisi, Manon Alkema, Amrita Chandrasekar, Peter C. Bull, Philip Bejon, Katarzyna Modrzynska, Teun Bousema, Matthias Marti
Summary: The malaria parasite life cycle involves asexual replication in human blood and differentiation into gametocytes for transmission to mosquitoes. Host factors influence the commitment to differentiate into gametocytes, but the exact mechanism is still unclear. In this study, we analyzed data from 828 children in Kenya over 18 years to understand the relationship between host immunity, parasite growth, and transmission investment. We found that reduced plasma lysophosphatidylcholine levels, which are associated with inflammatory responses, are correlated with increased transmission investment and reduced asexual replication.
Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Dennis O. Odera, James Tuju, Kennedy Mwai, Irene N. Nkumama, Kristin Fuerle, Timothy Chege, Rinter Kimathi, Stefan Diehl, Fauzia K. Musasia, Micha Rosenkranz, Patricia Njuguna, Mainga Hamaluba, Melissa C. Kapulu, Roland Frank, Faith H. A. Osier
Summary: NK cells can be activated through Fc receptor engagement by antibodies, leading to degranulation and IFN-gamma release upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK activity plays a crucial role in controlling parasitemia after experimental malaria challenge in adults and reducing the risk of clinical episodes of malaria in children. Several vaccine candidates, including less characterized antigens such as P41, P113, MSP11, RHOPH3, and Pf_11363200, induce antibody-dependent NK response, suggesting their potential in evaluating malaria vaccines.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Naoyuki Iso-o, Keisuke Komatsuya, Fuyuki Tokumasu, Noriko Isoo, Tomohiro Ishigaki, Hiroshi Yasui, Hiroshi Yotsuyanagi, Masumi Hara, Kiyoshi Kita
Summary: Malaria parasites require host cholesterol for multiplication in erythrocytes, and a novel HDL-delivery pathway involving exosomes and scavenger receptors may facilitate this process. Platelet-derived exosomes containing CD36 can potentially deliver cholesterol to parasites, explaining the first step of sterol uptake by intracellular parasites.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Brendan Fries, Carlos A. Guerra, Guillermo A. Garcia, Sean L. Wu, Jordan M. Smith, Jeremias Nzamio Mba Oyono, Olivier T. Donfack, Jose Osa Osa Nfumu, Simon Hay, David L. Smith, Andrew J. Dolgert
Summary: Different population layers performed differently in matching the gold standard distribution at different population densities. Choosing the appropriate population map has a significant impact on burden estimates in a malaria model.
Article
Biology
Emily R. Ebel, Frans A. Kuypers, Carrie Lin, Dmitri A. Petrov, Elizabeth S. Egan
Summary: The study on 121 healthy donors of African ancestry found that various genes and phenotypes related to red blood cell variation were closely associated with the adaptability of Plasmodium falciparum within red blood cells, indicating globally widespread variations play a role in modulating parasite fitness.
Article
Multidisciplinary Sciences
Theresa Reiker, Monica Golumbeanu, Andrew Shattock, Lydia Burgert, Thomas A. Smith, Sarah Filippi, Ewan Cameron, Melissa A. Penny
Summary: Individual-based models are essential in the global fight against infectious diseases, but the complexity of the models can pose challenges for calibration. The authors propose using a Bayesian optimization framework to calibrate a complex malaria transmission simulator, resulting in improved fitting outcomes compared to previous calibrations.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Claudia B. G. Barnes, Madeline G. Dans, Thorey K. Jonsdottir, Brendan S. Crabb, Paul R. Gilson
Summary: Research has shown that certain PfATP4 inhibitors can prevent malaria parasites from escaping host red blood cells or entering new host cells. These compounds inhibit parasite egress by blocking the activation of protein kinase G, and there is a direct link between egress and the function of PfATP4. Additionally, these inhibitors can induce host cell lysis before parasite replication is complete.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Jean C. Digitale, Perri C. Callaway, Maureen Martin, George Nelson, Mathias Viard, John Rek, Emmanuel Arinaitwe, Grant Dorsey, Moses Kamya, Mary Carrington, Isabel Rodriguez-Barraquer, Margaret E. Feeney
Summary: The study identified a relationship between KIR and HLA genotypes and the risk of Plasmodium falciparum infection, where the presence of HLA-C2 and HLA-Bw4 increased the likelihood of infection, while HLA-C1 decreased it.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Christine R. Collins, Abigail J. Perrin, Konstantinos Koussis, Claudine Bisson, Michael J. Blackman, Aigars Jirgensons
Summary: Malaria is a devastating infectious disease causing over 400,000 deaths annually. Researchers have developed substrate-based peptidic boronic acids that inhibit a parasite protease called SUB1, preventing parasite replication through egress and potentially serving as a new class of antimalarial drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Summary: Severe malaria caused by Plasmodium falciparum is difficult to accurately diagnose in children in high-transmission settings. A combination of platelet count and plasma PfHRP2 concentration can be used to identify severe falciparum malaria in severely ill patients. About one-third of children enrolled in clinical studies of severe malaria in high-transmission settings in Africa had other causes of their severe illness.
SCIENCE TRANSLATIONAL MEDICINE
(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.
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
Biochemistry & Molecular Biology
Stephanie Studniberg, Lisa J. Ioannidis, Retno A. S. Utami, Leily Trianty, Yang Liao, Waruni Abeysekera, Connie S. N. Li-Wai-Suen, Halina M. Pietrzak, Julie Healer, Agatha M. Puspitasari, Dwi Apriyanti, Farah Coutrier, Jeanne R. Poespoprodjo, Enny Kenangalem, Benediktus Andries, Pak Prayoga, Novita Sariyanti, Gordon K. Smyth, Alan F. Cowman, Ric N. Price, Rintis Noviyanti, Wei Shi, Alexandra L. Garnham, Diana S. Hansen
Summary: This study investigates the differences between individuals experiencing symptomatic and asymptomatic P. falciparum infection using a systems approach. The results show that asymptomatic malaria, despite having protective responses, still exhibits an immunosuppressive transcriptional signature, which may impact the control of parasites and the response to malaria vaccines.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anthony N. Hodder, Janni Christensen, Stephen Scally, Tony Triglia, Anna Ngo, Richard W. Birkinshaw, Brodie Bailey, Paola Favuzza, Melanie H. Dietrich, Wai-Hong Tham, Peter E. Czabotar, Kym Lowes, Zhuyan Guo, Nicholas Murgolo, Manuel de Lera Ruiz, John A. McCauley, Brad E. Sleebs, David Olsen, Alan F. Cowman
Summary: Plasmepsins IX and X are essential proteases in Plasmodium spp., and their inhibition by WM4 and WM382 has been studied. The research identified protein substrates and revealed differences in substrate binding for PMIX and PMX. The structural analysis of PMX provided insights into drug binding important for drug development.
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
Chemistry, Medicinal
Lachlan W. Richardson, Trent D. Ashton, Madeline G. Dans, Nghi Nguyen, Paola Favuzza, Tony Triglia, Anthony N. Hodder, Anna Ngo, Kate E. Jarman, Alan F. Cowman, Brad E. Sleebs
Summary: Plasmepsin X is an important aspartyl protease in the invasion and egression of Plasmodium parasites. In this study, peptidomimetics were designed to inhibit Plasmepsin X and effectively arrested the development of asexual Plasmodium falciparum parasites. These findings are significant for understanding the substrate specificity of Plasmepsin X and designing future antimalarial drugs.
Article
Cell Biology
Oliver Looker, Madeline G. Dans, Hayley E. Bullen, Brad E. Sleebs, Brendan S. Crabb, Paul R. Gilson
Summary: This study identified a new compound that inhibits protein export in Plasmodium falciparum parasites, leading to reduced virulence and potential elimination of the parasites.
Article
Chemistry, Medicinal
Manuel de Lera Ruiz, Paola Favuzza, Zhuyan Guo, Lianyun Zhao, Bin Hu, Zhiyu Lei, Dongmei Zhan, Nicholas Murgolo, Christopher W. Boyce, Marissa Vavrek, Jennifer Thompson, Anna Ngo, Kate E. Jarman, Johnathan Robbins, Justin Boddey, Brad E. Sleebs, Kym N. Lowes, Alan F. Cowman, David B. Olsen, John A. McCauley
Summary: Drug resistance to antimalarials is increasing, highlighting the need for new drugs with novel mechanisms of action. A phenotypic screen identified a potent plasmepsin X inhibitor, which was further optimized to also inhibit plasmepsin IX. The resulting dual inhibitor showed excellent in vivo efficacy and resistance profile.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Melanie H. Dietrich, Mikha Gabriela, Kitsanapong Reaksudsan, Matthew W. A. Dixon, Li-Jin Chan, Amy Adair, Stephanie Trickey, Matthew T. O. 'Neill, Li Lynn Tan, Sash Lopaticki, Julie Healer, Sravya Keremane, Alan F. Cowman, Wai-Hong Tham
Summary: Transmission blocking interventions can effectively prevent the spread of malaria by inhibiting parasite infection in mosquitos. Pfs230, a member of the 6-cysteine protein family, is a leading candidate for a malaria transmission blocking vaccine. Researchers have identified high affinity Pfs230-specific nanobodies that can significantly block P. falciparum transmission and have gained insights into the mechanism of action of these nanobodies.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alan John, Stefanie M. Bader, Niccolay Madiedo Soler, Kharizta Wiradiputri, Swapnil Tichkule, Sean T. Smyth, Stuart A. Ralph, Aaron R. Jex, Nichollas E. Scott, Christopher J. Tonkin, Ethan D. Goddard-Borger
Summary: Cryptosporidium parvum is a common cause of diarrheal disease worldwide and developing vaccines to prevent or limit infection is important. The study investigates the architecture, conservation, and glycosylation of the CpTSP protein family in C. parvum. The results show that these proteins are modified with C-, O-, and N-linked glycans and are found on the cell surface and in secretory pathway-like structures. The study also reveals the presence of CpTSP1 in sporozoites and meronts, shedding new light on potential vaccine targets for cryptosporidiosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Parasitology
Fiona Angrisano, Amelia Ford, Andrew Michael Blagborough, Hayley Elise Bullen
Summary: Protein disulfide isomerases (PDIs) play a crucial role in ensuring the proper folding of specific substrate proteins and are important for malaria transmission. This article provides an overview of the involvement of PDIs in malaria-causing Plasmodium parasites and discusses the potential of PDI inhibition as a novel approach for malaria treatment and prevention.
TRENDS IN PARASITOLOGY
(2023)
Article
Multidisciplinary Sciences
Tony Triglia, Stephen W. Scally, Benjamin A. Seager, Michal Pasternak, Laura F. Dagley, Alan F. Cowman
Summary: The authors characterized the function of the aspartic protease PMX and its role in activating the PCRCR complex, which is involved in erythrocyte invasion by Plasmodium falciparum. This study provides important insights into the essential role of PMX and the fine regulation of PCRCR function in P. falciparum biology.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Mary-Louise Wilde, Ushma Ruparel, Theresa Klemm, V. Vern Lee, Dale J. Calleja, David Komander, Christopher J. Tonkin
Summary: The phylum Apicomplexa consists of several parasitic species that are medically and agriculturally important. Despite its crucial role in eukaryotic biology, the ubiquitination machinery in apicomplexan parasites remains largely uncharacterized. Bioinformatic analysis of this machinery in apicomplexan parasites identified an expanded family of ovarian tumour domain-containing (OTU) deubiquitinase (DUB) enzymes in Toxoplasma, suggesting their functional significance. This study provides a comprehensive characterization of Toxoplasma OTU DUBs, including the identification of apicomplexan-specific enzymes. The biochemical analysis revealed their activity against various ubiquitin- and NEDD8-based substrates and their preferences for different types of ubiquitin linkages.
LIFE SCIENCE ALLIANCE
(2023)
Article
Chemistry, Medicinal
Martin A. . Lowe, Alvaro Cardenas, Jean-Pierre Valentin, Zhaoning Zhu, Jan Abendroth, Jose L. Castro, Reiner Class, Annie Delaunois, Renaud Fleurance, Helga Gerets, Vitalina Gryshkova, Lloyd King, Donald D. Lorimer, Malcolm MacCoss, Julian H. Rowley, Marie-Luce Rosseels, Leandro Royer, Richard D. Taylor, Melanie Wong, Oliver Zaccheo, Vishal P. Chavan, Gokul A. . Ghule, Bapusaheb K. Tapkir, Jeremy N. Burrows, Maelle Duffey, Matthias Rottmann, Sergio Wittlin, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Josefine Striepen, Kate J. Fairhurst, Tomas Yeo, David A. . Fidock, Alan F. Cowman, Paola Favuzza, Benigno Crespo-Fernandez, Francisco Javier Gamo, Daniel E. Goldberg, Dominique Soldati-Favre, Benoit Laleu, Teresa de Haro
Summary: This study optimized Plasmepsin X (PMX) and identified potent PMX inhibitors with potential efficacy in treating malaria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)