Article
Medicine, General & Internal
Rebecca Webster, Silvana Sekuloski, Anand Odedra, Stephen Woolley, Helen Jennings, Fiona Amante, Katharine R. Trenholme, Julie Healer, Alan F. Cowman, Emily M. Eriksson, Priyanka Sathe, Jocelyn Penington, Adam J. Blanch, Matthew W. A. Dixon, Leann Tilley, Michael F. Duffy, Alister Craig, Janet Storm, Jo-Anne Chan, Krystal Evans, Anthony T. Papenfuss, Louis Schofield, Paul Griffin, Bridget E. Barber, Dean Andrew, Michelle J. Boyle, Fabian de Labastida Rivera, Christian Engwerda, James S. McCarthy
Summary: A genetically attenuated blood-stage malaria vaccine was developed and tested in healthy volunteers, showing immunogenicity but causing significant parasitemia at high doses.
Editorial Material
Parasitology
Kwesi Z. Tandoh, Collins M. Moranga, Michael Wilson, Neils B. Quashie, Nancy O. Duah-Quashie
Summary: Plasmodium falciparum, the cause of malaria, is developing resistance to artemisinin, a drug used to treat malaria, which threatens the effectiveness of malaria control. The development of artemisinin resistance may involve the role of extracellular vesicles in increasing oxidative stress tolerance and reducing the trafficking of hemoglobin to the food vacuole.
TRENDS IN PARASITOLOGY
(2022)
Review
Microbiology
Paulo O. L. Moreira, Paula M. Nogueira, Rubens L. Monte-Neto
Summary: Despite decades of research, a safe and effective vaccine for leishmaniasis is still lacking. Therefore, finding a new prophylaxis alternative for controlling leishmaniasis should be a global priority.
Article
Multidisciplinary Sciences
Paulina Tindana, Rosemonde Guissou, Oladimeji Akeem Bolarinwa, Fatoumata Tou, Freek de Haan, Mehul Dhorda, Arjen M. Dondorp, Chanaki Amaratunga, Olugbenga Ayodeji Mokuolu, Jean Bosco Ouedraogo, Phaik Yeong Cheah
Summary: This paper presents an analysis of stakeholders' perspectives regarding key ethical considerations to be considered in the deployment of triple artemisinin-based combination therapies (TACTs) in Africa. Engagement with stakeholders and addressing ethical issues will be crucial for potential deployment of TACTs in Africa.
Article
Multidisciplinary Sciences
Tran Dang Nguyen, Bo Gao, Chanaki Amaratunga, Mehul Dhorda, Thu Nguyen-Anh Tran, Nicholas J. White, Arjen M. Dondorp, Maciej F. Boni, Ricardo Aguas
Summary: Triple artemisinin-based combination therapies (TACTs) have shown high efficacy for the treatment of malaria and could delay the emergence and spread of artemisinin resistance, improving treatment outcomes and the chances of malaria elimination.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Blandine Franke-Fayard, Catherin Marin-Mogollon, Fiona J. A. Geurten, Severine Chevalley-Maurel, Jai Ramesar, Hans Kroeze, Els Baalbergen, Els Wessels, Ludivine Baron, Valerie Soulard, Thomas Martinson, Maya Aleshnick, Antonius T. G. Huijs, Amit K. Subudhi, Yukiko Miyazaki, Ahmad Syibli Othman, Surendra Kumar Kolli, Olivia A. C. Lamers, Magali Roques, Rebecca R. Stanway, Sean C. Murphy, Lander Foquet, Diana Moita, Antonio M. Mendes, Miguel Prudencio, Koen J. Dechering, Volker T. Heussler, Arnab Pain, Brandon K. Wilder, Meta Roestenberg, Chris J. Janse
Summary: This study describes the generation of a potential LA-GAP for malaria through gene deletion, which showed growth arrest in a human liver-chimeric mouse model and sensitivity to antimalarial drugs. The findings support further clinical evaluation of this mutant.
Article
Immunology
Naoyuki Fukuda, Betty Balikagala, Tsuyoshi Ueno, Denis A. Anywar, Eisaku Kimura, Nirianne Marie Q. Palacpac, Emmanuel Odongo-Aginya, Martin Ogwang, Toshihiro Horii, Takashi Miida, Toshihiro Mita
Summary: The study found that mature Plasmodium falciparum parasites are rarely found in the peripheral blood because they are sequestered and attached to the endothelium. Intensive sequestration is associated with a delay in parasite clearance after artemisinin-based treatment. Sequestration plays an important role in the efficacy of artemisinin treatment for malaria.
CLINICAL INFECTIOUS DISEASES
(2023)
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
Chemistry, Medicinal
Edwin G. Tse, Laksh Aithani, Mark Anderson, Jonathan Cardoso-Silva, Giovanni Cincilla, Gareth J. Conduit, Mykola Galushka, Davy Guan, Irene Hallyburton, Benedict W. J. Irwin, Kiaran Kirk, Adele M. Lehane, Julia C. R. Lindblom, Raymond Lui, Slade Matthews, James McCulloch, Alice Motion, Ho Leung Ng, Mario Oeren, Murray N. Robertson, Vito Spadavecchio, Vasileios A. Tatsis, Willem P. van Hoorn, Alexander D. Wade, Thomas M. Whitehead, Paul Willis, Matthew H. Todd
Summary: The research aims to develop compounds to kill the malaria parasite by targeting PfATP4. They organized a public competition, and the best models were used to predict and synthesize novel inhibitors with biological activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Lekkala Ravindar, Siti Aishah Hasbullah, K. P. Rakesh, Nurul Izzaty Hassan
Summary: Malaria is a deadly parasitic infection ranked as the fifth most lethal worldwide. Antimalarial medications are crucial for preventing and eradicating malaria. The 4-aminoquinoline moiety has diverse biological applications and has been favored in antimalarial drug discovery. This review focuses on its efficacy when hybridized with various heterocyclic scaffolds, aiding the development of more effective antimalarial agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jacqueline Araujo Fiuza, Sreenivas Gannavaram, Soraya Torres Gaze, Leticia Gambogi de Ornellas, Erica Alessandra Alves, Nevien Ismail, Hira Lal Nakhasi, Rodrigo Correa-Oliveira
Summary: Vaccination with centrin-deleted Leishmania parasites against visceral leishmaniasis has been extensively studied. The protection induced by this vaccine is mediated by CD4(+) and CD8(+) T cells. However, the specific parasite determinants affecting these T cell populations remain unknown.
SCIENTIFIC REPORTS
(2023)
Article
Parasitology
Koketso S. P. Mogwera, Kelly Chibale, Lauren B. Arendse
Summary: The protein and phosphoinositide kinase gene families are highly druggable and essential in cellular life, providing potential targets for pharmacological modulation in various diseases. However, targeting kinases comes with challenges of selectivity and acquired resistance. The success of a kinase inhibitor in malaria treatment shows the potential benefits of Plasmodium kinase inhibitors and the opportunity for reducing resistance through designed polypharmacology.
TRENDS IN PARASITOLOGY
(2023)
Article
Immunology
Marie Mura, Tanmaya Atre, Tatyana Savransky, Elke S. Bergmann-Leitner
Summary: The beginning of an adaptive immune response determines the fate of antigen-specific lymphocytes, with the expression of homing receptors being crucial. A radiation-attenuated malaria vaccine was used as a model to investigate the induction of specific homing receptors by the parasite delivered through mosquito bite, providing insights for malaria vaccine development. The infection with live sporozoites triggers the upregulation of different homing receptors compared to attenuated sporozoites, suggesting the presence of additional signals that prime lymphocytes for homing to the liver.
Article
Medicine, General & Internal
Dorothea Ekoka Mbassi, Ghyslain Mombo-Ngoma, Jana Held, Dearie Glory Okwu, Wilfrid Ndzebe-Ndoumba, Laura Charlotte Kalkman, Franck Aurelien Ekoka Mbassi, Lais Pessanha de Carvalho, Juliana Inoue, Malik Azeez Akinosho, Lia Betty Dimessa Mbadinga, Emmanuel Koffi Yovo, Benjamin Mordmueller, Peter Gottfried Kremsner, Ayola Akim Adegnika, Michael Ramharter, Rella Zoleko-Manego
Summary: This study assessed the tolerability and efficacy of ivermectin in Gabonese adults with P. falciparum infections. The results showed that ivermectin reduced the asexual parasites similarly to placebo, indicating its potential as a treatment for asymptomatic P. falciparum infections.
Article
Biochemistry & Molecular Biology
Ali Altharawi, Yassine Riadi, Muhammad Tahir ul Qamar
Summary: The emergence of artemisinin resistance by malaria parasites is a major challenge in the fight against malaria. To tackle this, antimalarial drugs with unconventional mechanisms are urgently needed. Blocking the function of hexose transporter 1 (PfHT1) protein, the only known transporter for glucose uptake in Plasmodium falciparum, can selectively starve the parasites and provide an alternative approach to fight drug-resistant malaria.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Microbiology
Ganesh Ram R. Visweswaran, Kamalakannan Vijayan, Ramyavardhanee Chandrasekaran, Olesya Trakhimets, Samantha L. Brown, Vladimir Vigdorovich, Ashton Yang, Andrew Raappana, Alex Watson, William Selman, Meghan Zuck, Nicholas Dambrauskas, Alexis Kaushansky, D. Noah Sather
Summary: This study compared antibody and B cell responses in two mouse strains with different abilities to generate protective antibodies against malaria infection. The presence of vaccine-elicited antibodies was shown to be responsible for protection, and the ability of antibodies to neutralize the parasite was directly linked to their affinity to CSP. The study found that germinal center activity, a key process in B cell maturation, was significantly diminished in the non-protected mouse strain. Additionally, higher levels of somatic mutation, a result of germinal center activity, were observed in the protected mice. These results suggest that enhanced B cell maturation is linked to the ability to generate protective antibody responses, providing important information for the development of future vaccines.
Article
Cell Biology
Arti T. Navare, Fred D. Mast, Jean Paul Olivier, Thierry Bertomeu, Maxwell L. Neal, Lindsay N. Carpp, Alexis Kaushansky, Jasmin Coulombe-Huntington, Mike Tyers, John D. Aitchison
Summary: Using a viral-induced hypomorph of GBF1, this study demonstrates that the principle of synthetic lethality can selectively kill virus-infected cells. Viral protein interactions can induce hypomorphs in host cells, making them selectively vulnerable to perturbations.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Immunology
Christoph C. Carter, Fred D. Mast, Jean Paul Olivier, Natasha M. Bourgeois, Alexis Kaushansky, John D. Aitchison
Summary: This study reveals the important role of mTORC2 in dengue replication. It is not only activated during viral replication, but also promotes the survival of infected cells by inhibiting apoptosis, maximizing viral replication.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Julie Healer, Jennifer K. K. Thompson, Karen L. L. Mackwell, Cecille D. D. Browne, Benjamin A. A. Seager, Anna Ngo, Kym N. N. Lowes, Sarah E. E. Silk, David Pulido, Lloyd D. W. King, Jayne M. M. Christen, Amy R. R. Noe, Vinayaka Kotraiah, Paul J. J. Masendycz, Rajkannan Rajagopalan, Leanne Lucas, Marianne M. M. Stanford, Lorraine Soisson, Carter Diggs, Robin Miller, Susan Youll, Kaye Wycherley, Simon J. J. Draper, Alan F. F. Cowman
Summary: This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr, and CyRPA. The results showed that this vaccine could induce highly inhibitory parasite neutralizing antibodies against Plasmodium falciparum.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Stephen W. Scally, Tony Triglia, Cindy Evelyn, Benjamin A. Seager, Michal Pasternak, Pailene S. Lim, Julie Healer, Niall D. Geoghegan, Amy Adair, Wai-Hong Tham, Laura F. Dagley, Kelly L. Rogers, Alan F. Cowman
Summary: This study identified the importance of the PCRCR complex, consisting of PfPTRAMP and PfCSS, in the invasion of erythrocytes by Plasmodium falciparum. The PCRCR complex plays a role in anchoring the contact between merozoite and erythrocyte membranes, facilitated by strong parasite deformations. In addition, the study identified inhibitory epitopes, which can guide the development of a malaria vaccine targeting the blood stage.
NATURE MICROBIOLOGY
(2022)
Editorial Material
Parasitology
Alexis Kaushansky, Nana Minkah
Summary: Chora and colleagues have demonstrated that liver infection in severe malaria cases modulates the severity of the experimental cerebral malaria (ECM) model by generating gamma delta (y delta) T cells that produce IL-17. This research challenges the long-standing assumption that liver infection does not influence the severity of malaria.
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
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)
Article
Biochemical Research Methods
Zephyr Pitre, Tess Seltzer, Cecilia Kalthoff, Maria Benitez-Cortez, Conrad Yee, Elizabeth K. K. Glennon, Veronica I. Primavera, Alexis Kaushansky
Summary: This article presents a protocol for assembling and implementing a partially automated system for rearing and handling Anopheles stephensi mosquitoes, which can be used to study vector-borne diseases. The specific limitations of these systems are also discussed.
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)
Article
Biochemistry & Molecular Biology
Kamalakannan Vijayan, Nadia Arang, Ling Wei, Robert Morrison, Rechel Geiger, K. Rachael Parks, Adam J. Lewis, Fred D. Mast, Alyse N. Douglass, Heather S. Kain, John D. Aitchison, Jarrod S. Johnson, Alan Aderem, Alexis Kaushansky
Summary: This study revealed that host microtubules dynamically reorganize around the developing liver stage parasite to facilitate vesicular transport. Through a genome-wide screen, regulators of cytoskeleton organization, vesicle trafficking, and ER/Golgi stress that regulate liver stage development were identified. The study also found that the Golgi acts as a non-centrosomal microtubule organizing center, promoting microtubule nucleation at the parasite periphery. These findings highlight the importance of host organelles in Plasmodium development.
CELL CHEMICAL BIOLOGY
(2022)