Article
Immunology
Margaux Chauvet, Cerina Chhuon, Joanna Lipecka, Sebastien Dechavanne, Celia Dechavanne, Murielle Lohezic, Margherita Ortalli, Damien Pineau, Jean-Antoine Ribeil, Sandra Manceau, Caroline Le Van Kim, Adrian J. F. Luty, Florence Migot-Nabias, Slim Azouzi, Ida Chiara Guerrera, Anais Merckx
Summary: This passage discusses the possible reasons for the high prevalence of sickle cell disease in certain populations may be related to the protective effect of HbS against severe malaria caused by Plasmodium falciparum. By studying protein phosphorylation, it reveals the impact of HbS heterozygous carriage on the phosphorylation of proteins in red blood cell membranes and skeletal proteins, as well as parasite proteins during infection with malaria, which may lead to a less severe manifestation of malaria symptoms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Brittany N. Araj, Bruce Swihart, Robert Morrison, Patricia Gonzales Hurtado, Andrew Teo, Almahamoudou Mahamar, Oumar Attaher, Bacary S. Diarra, Santara Gaoussou, Djibrilla Issiaka, Alassane Dicko, Patrick E. Duffy, Michal Fried
Summary: The study utilized proteomic analyses of PfEMP1 from clinical parasite isolates collected from Malian children to identify targets of immunity. Peptide-specific antibody responses in children were examined, and it was found that high antibody levels to specific PfEMP1 domains correlated with decreased parasite burden in future infections. These findings suggest that certain PfEMP1 domains play a role in protective immunity against malaria.
Article
Multidisciplinary Sciences
Raj Kumar Sah, Soumya Pati, Monika Saini, Shailja Singh
Summary: The sphingolipid pool plays a crucial role in regulating cellular functions in Plasmodium falciparum, and the parasite co-opts sphingolipids from host erythrocytes for its growth. By inhibiting SphK, the growth and development of P. falciparum can be inhibited, highlighting the importance of endogenous S1P in erythrocytes for parasite growth. Plasma S1P levels have no significant effect on Plasmodium growth, indicating a host-mediated effect.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Josie L. Ferreira, Vojtech Prazak, Daven Vasishtan, Marc Siggel, Franziska Hentzschel, Annika M. Binder, Emma Pietsch, Jan Kosinski, Friedrich Frischknecht, Tim W. Gilberger, Kay Gruenewald
Summary: Microtubules in Plasmodium falciparum exhibit diverse structures coordinated by unique organizing centers at different stages of its life cycle. This unusual microtubule cytoskeleton has not been observed in any other organism to date, highlighting its importance in understanding the pathogenicity of the malaria parasite.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Gavin Band, Ellen M. Leffler, Muminatou Jallow, Fatoumatta Sisay-Joof, Carolyne M. Ndila, Alexander W. Macharia, Christina Hubbart, Anna E. Jeffreys, Kate Rowlands, Thuy Nguyen, Sonia Goncalves, Cristina Ariani, Jim Stalker, Richard D. Pearson, Roberto Amato, Eleanor Drury, Giorgio Sirugo, Umberto D'Alessandro, Kalifa A. Bojang, Kevin Marsh, Norbert Peshu, Joseph W. Saelens, Mahamadou Diakite, Steve M. Taylor, David J. Conway, Thomas N. Williams, Kirk A. Rockett, Dominic P. Kwiatkowski
Summary: This study found a strong association between host sickle haemoglobin (HbS) and three regions of the parasite genome, which is replicated in additional samples. The protective effect of HbS against severe malaria varies greatly according to the parasite genotype at these three loci, suggesting an evolutionary adaptation of parasite populations to host genetic factors.
Article
Biology
J. Stephan Wichers, Gerry Tonkin-Hill, Thorsten Thye, Ralf Krumkamp, Benno Kreuels, Jan Strauss, Heidrun von Thien, Judith A. M. Scholz, Helle Smedegaard Hansson, Rasmus Weisel Jensen, Louise Turner, Freia-Raphaella Lorenz, Anna Schollhorn, Iris Bruchhaus, Egbert Tannich, Rolf Fendel, Thomas D. Otto, Thomas Lavstsen, Tim W. Gilberger, Michael F. Duffy, Anna Bachmann
Summary: The study found that parasite with PfEMP1 variants that bind to the endothelial protein C receptor (EPCR) were associated with severe malaria, while those binding to CD36 were linked to non-severe outcomes. First-time infected adults are more likely to develop severe symptoms, indicating that certain pathogenic PfEMP1 variants are more common in patients with naive immune systems.
Article
Biochemistry & Molecular Biology
Rakhee Lohia, Benoit Allegrini, Laurence Berry, Helene Guizouarn, Rachel Cerdan, Manouk Abkarian, Dominique Douguet, Eric Honore, Kai Wengelnik
Summary: A gain-of-function variant (E756del) in the PIEZO1 channel prevents severe malaria. Activation of PIEZO1 by Yoda1 and Jedi2 inhibitors induces echinocytosis and dehydration of red blood cells, inhibiting invasion by Plasmodium falciparum.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Microbiology
James S. McCarthy, Azrin N. Abd-Rahman, Katharine A. Collins, Louise Marquart, Paul Griffin, Anne Kummel, Aline Fuchs, Cornelis Winnips, Vishal Mishra, Katalin Csermak-Renner, J. Prakash Jain, Preetam Gandhi
Summary: The new antimalarial compound cipargamin showed antimalarial activity in healthy volunteers infected with blood-stage Plasmodium falciparum, although some subjects experienced serious liver function changes during treatment. Further evaluation of the compound's hepatic safety profile is needed despite the promising antimalarial activity observed.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Bridget E. Barber, Azrin N. Abd-Rahman, Rebecca Webster, Adam J. Potter, Stacey Llewellyn, Louise Marquart, Nischal Sahai, Indika Leelasena, Geoffrey W. Birrell, Michael D. Edstein, G. Dennis Shanks, David Wesche, Joerg J. Moehrle, James S. McCarthy
Summary: A single oral dose of tafenoquine is effective against blood-stage Plasmodium falciparum infection, but prior screening for glucose 6-phosphate dehydrogenase deficiency is necessary due to the estimated dose required to clear asexual parasitaemia being >= 460 mg (in adults).
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Jessica N. McCaffery, Douglas Nace, Camelia Herman, Balwan Singh, Eric Mukomena Sompwe, Papy Mandoko Nkoli, Dieudonne Mumba Ngoyi, Gauthier Mesia Kahunu, Eric S. Halsey, Eric Rogier
Summary: A study conducted in the Democratic Republic of the Congo found a low prevalence of pfhrp2 and pfhrp3 gene deletions in blood samples from patients with Plasmodium falciparum infection. Single deletions of pfhrp2 and pfhrp3 were sporadically observed in the study sites, while dual deletions were not found. The use of HRP2-based RDTs still appears to be appropriate for these locations in DRC.
SCIENTIFIC REPORTS
(2021)
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
Immunology
Gladys J. Keitany, Bethany J. Jenkins, Harold T. Obiakor, Shaji Daniel, Atis Muehlenbachs, Jean-Philippe Semblat, Benoit Gamain, Justin Y. A. Doritchamou, Sanjay A. Desai, Nicholas J. MacDonald, David L. Narum, Robert Morrison, Tracy Saveria, Marissa Vignali, Andrew Oleinikov, Michal Fried, Patrick E. Duffy
Summary: This study characterizes an invariant protein associated with placental malaria (PM), PfCSA-L, which binds both VAR2CSA and placental CSA with high affinity. Unlike VAR2CSA, PfCSA-L is peripherally associated with the outer surface of knobs through protein-protein interactions with VAR2CSA. The findings suggest that sequestration of infected red blood cells (iRBCs) involves complexes of invariant and variant surface proteins, allowing parasites to maintain diversity and function on the iRBC surface.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Parasitology
Mia Andrews, Jake Baum, Paul R. Gilson, Danny W. Wilson
Summary: This article discusses recent evidence and re-evaluates previous data regarding the invasion of red blood cells by malaria parasite merozoites. It suggests that merozoites are capable of motility and have spherical or elongated-teardrop shapes. Furthermore, the article highlights that merozoites invade red blood cells 'wider end' first and pack within schizonts with this wider end facing outwards.
TRENDS IN PARASITOLOGY
(2023)
Article
Immunology
Hina Singh, Syed Yusuf Mian, Alok K. Pandey, Sri Krishna, Gaurav Anand, K. Sony Reddy, Neha Chaturvedi, Vanndita Bahl, Nidhi Hans, Man Mohan Shukla, Quique Bassat, Alfredo Mayor, Kazutoyo Miura, Praveen K. Bharti, Carole Long, Neeru Singh, Virander Singh Chauhan, Deepak Gaur
Summary: This study evaluated 25 triple antibody combinations for parasite neutralization activity against clinical isolates and identified the MSP-Fu+CyRPA+RH5 antibody combination as having the maximal neutralization effect against variable P. falciparum parasites. This suggests that these antibody combinations could be promising candidate antigens for a potential blood-stage malaria vaccine.
JOURNAL OF INFECTIOUS DISEASES
(2021)
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
Biochemistry & Molecular Biology
Susanne Schipper, Hanzhi Wu, Cristina M. Furdui, Leslie B. Poole, Claire M. Delahunty, Robin Park, John R. Yates, Katja Becker, Jude M. Przyborski
Summary: This study established an optimized method to rapidly capture sulfenylated proteins and identified 102 proteins containing 152 sulfenylation sites in Plasmodium falciparum trophozoites, showing common core proteins undergoing redox regulation by multiple mechanisms. The findings provide a basis for further exploration of the structural and biochemical basis of regulation, and a deeper understanding of crosstalk between post-translational modifications.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Multidisciplinary Sciences
Maneesh K. Singh, Giulliana Tessarin-Almeida, Barbara K. M. Dias, Pedro Scarpellli Pereira, Fahyme Costa, Jude M. Przyborski, Celia R. S. Garcia
Summary: The study demonstrates the significant role of the nuclear protein PfMORC in regulating the asexual cycle of the malaria parasite, with its expression being influenced by melatonin. PfMORC, in conjunction with melatonin signaling pathways, is essential for parasite synchronization.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Cecilia P. Sanchez, Pintu Patra, Shih-Ying Scott Chang, Christos Karathanasis, Lukas Hanebutte, Nicole Kilian, Marek Cyrklaff, Mike Heilemann, Ulrich S. Schwarz, Mikhail Kudryashev, Michael Lanzer
Summary: KAHRP plays a key role in Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, anchoring parasite-encoded adhesins to the membrane skeleton. Through super-resolution microscopy, it was found that KAHRP initially associates with various skeletal components before eventually colocalizing with remnant actin junctions under the spiral scaffold forming knobs. Additionally, a dynamic model of KAHRP organization and its function in attaching other factors to the spiral scaffold was proposed based on the findings.
MOLECULAR MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Patricia M. Dijkman, Tanja Marzluf, Yingyi Zhang, Shih-Ying Scott Chang, Dominic Helm, Michael Lanzer, Hermann Bujard, Mikhail Kudryashev
Summary: The study presents the structure of the merozoite surface protein 1 (MSP-1), revealing an unusual fold and dimerization capability. Dimerization of MSP-1 is concentration-dependent and can be influenced by interactions with the erythrocyte cytoskeleton protein spectrin. These findings provide insights into how MSP-1 may interact with erythrocytes and lay the groundwork for further research on its role in Plasmodium infection and immunity.
Article
Biochemistry & Molecular Biology
Kim C. Heimsch, Christoph G. W. Gertzen, Anna Katharina Schuh, Thomas Nietzel, Stefan Rahlfs, Jude M. Przyborski, Holger Gohlke, Markus Schwarzlaender, Katja Becker, Karin Fritz-Wolf
Summary: This study describes an improved redox biosensor, sfroGFP2, which can be used to measure oxidative effects within small cells. sfroGFP2 exhibits improved fluorescence intensity and structural stability, making it of significant interest for studying oxidative processes in small cells such as Plasmodium.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Aiyada Aroonsri, Chayaphat Wongsombat, Philip Shaw, Siegrid Franke, Jude Przyborski, Annette Kaiser
Summary: Treatment of protozoal infections is challenging due to drug shortages and increasing resistance, but recent progress has been made through parasite genome sequencing and validation of new targets. Posttranslational modification of a novel amino acid, hypusine, has potential as a drug target. Experimental results with human dhs inhibitors in Plasmodium show promising antimalarial activity, but further research is needed.
Article
Parasitology
Susanne Schipper, Eric Springer, Julia Hahn, Stefan Rahlfs, Priscila Bourilhon, Jurgen Bernhagen, Katja Becker, Jude M. Przyborski
Summary: PfMIF is a homologue of the human cytokine MIF and acts as a virulence factor in the malaria parasite Plasmodium falciparum, modulating the host immune system. It has DNase activity on human genomic DNA and binds to human chemokine receptors CXCR4 and CXCR2, which are non-cognate receptors for HsMIF. Additionally, post-translational modifications like S-glutathionylation and S-nitrosation affect receptor activation without impairing the enzyme activity of PfMIF.
PARASITOLOGY INTERNATIONAL
(2022)
Article
Cell Biology
Gabriele Kollisch, Francisco Venegas Solis, Hannah-Lena Obermann, Jeannine Eckert, Thomas Mueller, Tim Vierbuchen, Thomas Rickmeyer, Simon Muche, Jude M. Przyborski, Holger Heine, Andreas Kaufmann, Stefan Baumeister, Klaus Lingelbach, Stefan Bauer
Summary: In this study, nucleoside MTI is identified as a specific agonist for Toll-like receptor 8 (TLR8) derived from the malaria-causing pathogen P. falciparum. Co-incubation of MTI with TLR8 enhancer poly(dT) or synthetic/P. falciparum-derived RNA significantly enhances its stimulatory activity. These findings suggest that MTI is a natural immune recognition molecule for P. falciparum.
Article
Biochemical Research Methods
Julia Jaeger, Pintu Patra, Cecilia P. Sanchez, Michael Lanzer, Ulrich S. Schwarz
Summary: Malaria is a deadly infectious disease caused by a parasite that multiplies within red blood cells. Researchers have developed a computational model to predict the changes in mechanical properties and protein distribution in infected red blood cells. Their simulations show that specific proteins can relocate on the red blood cell surface due to changes in binding affinities, in agreement with experimental observations. This model can provide further insights into the mechanism of malaria parasite attack on red blood cell cytoskeleton.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biology
Jessica Jin, Mame Aida Ba, Chi Ho Wai, Sanjib Mohanty, Praveen K. Sahu, Rajyabardhan Pattnaik, Lukas Pirpamer, Manuel Fischer, Sabine Heiland, Michael Lanzer, Friedrich Frischknecht, Ann-Kristin Mueller, Johannes Pfeil, Megharay Majhi, Marek Cyrklaff, Samuel C. Wassmer, Martin Bendszus, Angelika Hoffmann
Summary: This study shows that reversible brain swelling in experimental murine cerebral malaria (CM) can be induced reliably after single vaccination with radiation-attenuated sporozoites, and it is suggested that transcellular blood-brain barrier disruption (BBBD) is responsible for the brain swelling. Although brain swelling can be reversed, it does not prevent persistent focal brain damage in the areas of most severe BBBD.
LIFE SCIENCE ALLIANCE
(2022)
Article
Microbiology
Cecilia P. Sanchez, Erin D. T. Manson, Sonia Moliner Cubel, Luis Mandel, Stefan K. Weidt, Michael P. Barrett, Michael Lanzer
Summary: The chloroquine resistance transporter, PfCRT, is crucial for the survival and development of the Plasmodium falciparum parasite. It plays a role in drug resistance and is responsible for transporting compounds targeting hemoglobin degradation. The natural function of PfCRT has been unclear, but this study provides evidence that it is involved in oligopeptide transport, contributing to nutrient acquisition and colloid osmotic balance.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Marvin Haag, Jessica Kehrer, Cecilia P. Sanchez, Marcel Deponte, Michael Lanzer
Summary: In this study, the redox potential of P. falciparum-infected erythrocytes was measured using parasite-encoded roGFP2 variants. The results showed a sudden shift from a reducing to an oxidizing environment in the infected erythrocytes, which was independent of the presence of hemoglobin S.
Article
Microbiology
Guillermo Gomez, Giulia A. D'Arrigo, Cecilia Sanchez, Fiona A. Berger, Rebecca Wade, Michael A. Lanzer
Summary: The PfCRT protein confers resistance to a wide range of antimalarial drugs. This study shows that both CQ- and PPQ-resistance conferring variants of PfCRT can bind and transport both drugs, but with subtle differences in kinetics. It also demonstrates the potential for engineering PfCRT variants with equal transport efficiencies for both PPQ and CQ.
Article
Multidisciplinary Sciences
Fiona Berger, Guillermo M. Gomez, Cecilia P. Sanchez, Britta Posch, Gabrielle Planelles, Farzin Sohraby, Ariane Nunes-Alves, Michael Lanzer
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Micha Rosenkranz, Kristin Fuerle, Julia Hibbert, Anne Ulmer, Arin Ali, Thomas Giese, Antje Blank, Walter E. Haefeli, Ernst Boehnlein, Michael Lanzer, Richard Thomson-Luque
Summary: Effective control of malaria requires a vaccine that targets both the liver stages and blood stages of the parasite Plasmodium falciparum. While progress has been made in liver stage vaccines, development of a blood stage vaccine is lagging. A new vaccine called SumayaVac-1 has been shown to elicit a strong immune response, including antibodies and T cell memory, and demonstrate multifunctional activity against malaria. Further evaluation in efficacy trials is warranted.
